Please use this identifier to cite or link to this item:
Pathophysiological Studies of Rabbit Hemorrhagic Disease: Changes in Hematology, Serum Chemistry, Electrolyte Balances and Alpha-fetoprotein Levels
|關鍵字:||Rabbit Hemorrhagic Disease;兔出血熱病;Hematology;Serum Chemistry;Electrolyte Balances;Alpha-fetoprotein;血液學;血清生化學;電解質;甲型胎兒蛋白質||出版社:||獸醫學系暨研究所||引用:||呂榮修. 1995. 台灣最近發生之禽畜疾病(參考手冊).台灣省畜牧獸醫學會. Aiyathurai, J. E. and Sentheshanmuganathan, S. 1976. The probable significance of hypertriglyceridemia in viral hepatitis. Aust. N. Z. J. Med. 6, 529-532. Alexandrov, M., Peshev, R., Yanchev, I., Bozhkov, S., Doumanova, L., Dimitrov, T. and Zacharieva, S. 1992. Immunohistochemical localization of the rabbit haemorrhagic disease viral antigen. Arch. Virol. 127: 355-363. Alonso, C., Oviedo, J. M., Martin-Alonao, J. M., Diaz, E., Boga, J. A. and Parra, F. 1998. Programmed cell death in the pathogenesis of rabbit hemorrhagic disease. Arch. Virol. 143: 321-332. Amarapurkar, D. N. and Amarapurkar, A. D. 2002. Extrahepatic manifestations of viral hepatitis. Ann. Hepatol. 1: 192-195. Baginski, I., Chemin, I., Bouffard, P., Hantz, O. and Trepo, C. 1991. Detection of polyadenilated RNA in hepatitis B virus infected peripheral blood mononuclear cells by polymerase chain reaction. J. Infect. Dis. 161: 996-1000. Bain, P. J. 2003. Liver. In: Latimer KS, Mahaffey EA, Prasse KW, ed. Veterinary laboratory medicine: clinical pathology. 4th ed. Harcourt Brace Jovanovich, Inc., 193-214. Balistreri, W. F. and Schubert, W. K. 1987. Liver disease in infancy and childhood. In Diseases of the Liver. 6th Edn. Eds. L. Schiff and E. R.Schiff. Philadelphia, J. B. Lippincott Company. pp 1337-1426. Barbieri, I., Lavazza, A., Brocchi, E., Konig, M. and Capucci, L. 1997. Morphological, structural and antigenic modifications of rabbit haemorrhagic disease virus in the course of the disease. Proceedings of the 1st Symposium on Calicivirus of the European Society of Veterinary Virology (ESVV), Reading, UK, 15-17 September 1996, 182-193. Boga, J. A., Marin, M. S., Casais, R., Prieto, M. and Parra, F. 1992. In vivtro translation of a sub-genomic mRNA from purified virions of the Spanish field isolate AST/89 of rabbit hemorrhagic disease virus (RHDV). Virus Research. 26: 33-40. Burkitt, H. G., Stevens, A., Lowe, J.S., and Young, B. 1996. Wheater’s Basic Histopathology. 3rd ed. Churchill Livingstone, Pearson Professional Limited, pp. 2-9. Burkitt, H.G., Young, B. and Heath, J. W. 1997. Wheater’s Functional Histology: A text and colour atlas. 3rd ed. Churchill Livingstone, Harcourrt Brace and Company Limited, pp. 2-30. Burrell, L. O. (Ed.) 1992. Adult nursing in hospital and community settings, E. Norwalk, CT: Appleton & Lange. 1738p. Bush, B. M. 1991. Interpretation of Laboratory Results for Small Animal Clinicians, Blackwell scientific publications, London. pp. 224-340. Capucci, L., Chasey, D., Lavazza, A. and Westcott, D. 1996a. Preliminary characterisation of a non-haemaggiutinating strain of rabbit haemorrhagic disease virus from the United Kingdom. J. Vet. Med. [B], 43: 245-250. Capucci, L., Fallacara, F., Grazioli, S., Lavazza,,A., Pacciarini, M. L. and Brocchi, E. 1998. A further step in the evolution of rabbit hemorrhagic disease virus: the appearance of the first consistent antigenic variant. Virus Res. 58: 115-126. Capucci, L., Frigoli, G., Ronsholt, L., Lavazza, A., Brocchi, E. and Rossi, C. 1995. Antigenicity of the rabbit hemorrhagic disease virus studied by its reactivity with monoclonal antibodies. Virus Res. 37: 221-238. Capucci, L., Fusi, P., Lavazza, A., Pacciarini, M. L. and Rossi, C. 1996b. Detection and preliminary characterization of a new rabbit calicivirus related to rabbit hemorrhagic disease virus but nonpathogenic. J. Virol. 70: 8614-8623. Capucci, L., Nardin, A. and Lavazza, A. 1997. Seroconversion in an industrial unit of rabbits infected with a non-pathogenic rabbit haemorrhagic disease-like virus. Vet. Rec. 140: 647-650. Capucci, L., Scicluna, M. T. and Lavazza, A. 1991. Diagnosis of viral haemorrhagic disease of rabbits and European brown hare syndrome. Rev. Sci. Tech. Off. Int. Epiz. 10: 347-370. Chasey, D., Trout, R. C. and Edwards, S. 1997. Susceptibility of wild rabbits (Oryctolagus cuniculus) in the united kingdom to rabbit haemorrhagic disease (RHD). Veterinary Research 28: 271-276. Cody, R. P. and Smith, J. K. 1987. Applied Statistics and the SAS Programming Language. 2nd ed., Elsevier Science Publishing Co., New York. Collins, B. J., White, J. R., Lenghaus, C., Morrissy, C. J. and Westbury, H. A. 1996. Presence of rabbit haemorrhage disease virus antigen in rabbit tissues as revealed by a monoclonal antibody dependent capture ELISA. J. Virol. Methods 58: 145-154. Collins, B. J., White, J. R., Lenguas, C., Boyd, V. and Westbury, H. A. 1995. A competition ELISA for the detection of antibodies to rabbit haemorrhagic disease virus. Vet. Microbiol. 43: 85-96. Cooke, B. D., Robinson, A. J., Merchant, J. C., Nardin, A. and Capucci, L. 2000. Use of ELISAs in field studies of rabbit haemorrhagic disease (RHD) in Australia. Epidemiol. Infect. 124: 563-576. Cooke, B.D. 2002. Rabbit haemorrhagic disease: field epidemiology and the management of wild rabbit population. Rev. Sci. Tech. Off. Int. Epiz. 21(2): 347-358. Crosby, T. K. and Mclennan, J. 1996. Potential Vectors of Rabbit Calicivirus Disease (RCD) in New Zealand. A review. MAF policy. MAF, Wellington, New Zealand. Davis, B. D., Dulbecco, R., Eisen, H. N., and Ginsberg, H. S. 1990. In: Microbiology. 4th ed. J. B. Lippincott Company. Philadelphia. pp. 791-793. Declarmen, M., Muguruza, S. R., Alonso, J. L., Muzouiz, J. L., Girones, O., and Haggar, A. 1994. The search for the virus which causes rabbit hemorrhagic disease (RHD) in the fox and the role of domestic Canidae in the transmitsion of the disease. Recueil Medecine Veterinaire 170: 841-845. Dufour, D. R., J. A. Lott, F. S. Nolte, D. R. Gretch, R. S. Koff, and L. B. Seeff. 2000. Diagnosis and monitoring of hepatic injury. I. Performance characteristics of laboratory tests. Clinical Chemistry 2000; 46(12): 2027-2049. Ferreira, P. G., Costa-E-Silva, A., Monteiro, E., Oliveira, M. J. and Aguas, A. P. 2004. Transient decrease in blood heterophils and sustained liver damage caused by calicivirus infection of young rabbits that are naturally resistant to rabbit haemorrhagic disease. Res. Vet. Sci. 76: 83-94. Ferreira, P. G., Costa-E-Silva, A., Monteiro, E., Oliveira, M. J. and Aguas, A. P. 2006a. Liver enzymes and ultrastructure in rabbit haemorrhagic disease (RHD). Vet. Res. Commun. 30: 393-401. Ferreira, P. G., Costa-e-Silva, A., Oliveira, M. J., Monteiro, E., Cunha, E. M. and Aguas, A. P. 2006b. Severe leukopenia and liver biochemistry changes in adult rabbits after calicivirus infection. Res. Vet. Sci. 80: 218-225. Fröllch, K., Kllma, F., and Dedek, J. 1998. Antibodies against rabbit hemorrhagic disease virus in free-ranging red foxes from Germany. J. Wildlife Diseases. 34(3): 436-442. Fuchs, A. and Weissenbock, H. 1992. Comparative histopathologyical study of rabbit haemorrhagic disease (RHD) and European brown hare syndrome (EBHS). J. Comp. Pathol. 107: 103-113. Gelmetti, D., Grieco, V., Rossi, C., Capucci, L. and Lavazza, A. 1998. Detection of rabbit haemorrhagic disease virus (RHDV) by in situ hybridization with a digoxigenin labelled RNA-probe. J. Virol. Methods 72: 219-226. Gitlin, N. 1982. The serum glutamic oxaloacetic transaminase/serum glutamic pyruvic transaminase ratio as a prognostic index in severe acute viral hepatitis. Am. J. Gastroenterol. 77, 2-4. Gould, A. R., Kattenbelt, J. A., Lenghaus, C., Morrissy, C., Chamberlain, T., Collins, B. J. and Westbury H. A. 1997. The complete nucleotide sequence of rabbit haemorrhagic disease virus (Czech strain V351): use of the polymerase chain reaction to detect replication in Australian vertebrates and analysis of viral population sequence variation. Virus Res. 47: 7-17. Granzow, H., Weiland, F., Strebelow, H.-G., Lu C. M. and Schirrmeier, H. 1996. Rabbit hemorrhagic disease virus (RHDV): ultrastructure and biochemical studies of typical and core-like particles present in liver homogenates. Virus Res. 41: 163-172. Gregg, D. A., House, C., Meyer, R. and Berninger, M. 1991. Viral haemorrhagic disease of rabbits in Mexico: epidemiology and viral characterization. Rev. Sci. Tech. Off. Int. Epiz., 10, 435-451. Gregg, G. A., and House, C. 1989. Necrotic hepatitis of rabbits in Mexiko: a parvovirus. Vet. Rec. 125: 603-604. Guittre, C., Baginski, I., Le Gall, G., Prave, M., Trepo, O. and Cova, L. 1995. Detection of rabbit haemorrhagic disease virus isolates and sequence comparison of the N-terminus of the capsid protein gene by the polymerase chain reaction. Res. Vet. Sci. 58: 128-132. Guittre, C., Ruvoen-Clouet, N., Barraud, L., Cherel, Y., Baginski, I., Prave, M., Gamiere, J. P., Trepo, C. and Cova, L. 1996. Early stages of rabbit haemorrhagic disease virus infection monitored by polymerase chain reaction. Xentraibl Veterinarmed B. 43: 109-118. Henning, J., Meers, J. and Davies, P. R. 2005a. Exposure of rabbits to by ultraviolet (UV) light-inactivated rabbit haemorrhagic disease virus (RHDV) and subsequent challenge with virulent virus. Epidemiol Infect. 133(4): 731-735. Henning, J., Schnitzler, F. R., Pfeiffer, D. U. and Davies, P. 2005b. Influence of weather conditions on fly abundance and its implications for transmission of rabbit haemorrhagic disease virus in the North Island of New Zealand. Medical and Veterinary Entomology. 19: 251-262. Kimura, T., Mitsui, I., Okada, Y., Furuya, T., Ochiai, K., Umemura, T. and Itakura, C. 2001. Distribution of rabbit haemorrhagic disease virus RNA in experimentally infected rabbits. J. Comp. Path. 124: 134-141. Kitau, M. J., Grint, P. C., Heath, R. B., Chart, T. 1988. Serum alphafetoprotein levels in subjects infected with hepatitis B virus. J. Med. Virol. 26: 437-442. Kovaliski, J. 1998. Monitoring the spread of rabbit hemorrhagic disease virus as a new biological agent for control of wild European rabbits in Australia. J. Wildlife Disease. 34 (3): 421-428. Kumar, V., Abbas, A. K., Fausto, N. and Perkins., J. A. 2005. Pathologic Basis of Disease. 7th ed. Elservier Inc. pp.338. Latimer, K. S., Mahaffey, E. A., and Prasse, K. W., 2003. Veterinary Laboratory Medicine: Clinical Pathology. 4th ed. Harcourt Brace Jovanovich, Inc. Iowa.Ames. pp.199. Lavazza, A., Scicluna, M. T. and Capucci, L. 1996. Susceptibility of hares and rabbits to the European Brown Hare Syndrome Virus (EBHSV) and Rabbit Hemorrhagic Disease Virus (RHDV) under experimental conditions. J. Vet. Med. [B] 43: 401-410. Lee, C. S. and Park, C. K. 1987. Aetiological studies on an acute fatal disease of Angora rabbits: so-called rabbit sudden death. Korean Journal Veterinary Research 27: 227-90. Leighton, F. A., Artois, M., Capucci, L., Gavier-Widén, D. and Morisse, J. P. 1995. Antibody response to Rabbit viral Hemorrhagic disease virus in red foxes (Vulpes vulpes) consuming livers of infected rabbits (Oryctolagus cuniculus). J. Wildlife Diseases. 31(4): 541-544. Liaw, Y. F., Tai, D. I., Chen, T. J., Chu, C. M. and Huang, M. J. 1986. Alpha- fetoprotein changes in the course of chronic hepatitis: relation to bridging hepatic necrosis and hepatocellular carcinoma. Liver 6: 133-137. Liu S. J., Xue, H. P., Pu, B. Q. and Quian, N. H. 1984. A new viral disease in rabbits. Anim. Hus. Vet. Med. 16: 253-255. Marcato, P. S., Benazzi, C. and Vecchi, G. 1991. Clinical and pathological features of viral haemorrhagic disease of rabbits and of the European brown hare syndrome. Rev. Sci. Tech. Off. Int. Epiz. 10: 371-392. Marchandeau, S., Chantal, J., Portejole, Y., Barraud, S. and Chaval, Y. 1998. Impact of viral hemorrhagic disease on a wild population of European rabbits in France. J. Wildlife Diseases 34(3): 429-435. Marin, M. S., Martin Alonso, J. M., Perez Ordoyo Garcia, L. I., Boga, J. A., Arguello-Villares, J. L., Casais, R., Venugopal, K., Jiang, W., Gould, E. A., Parra, F. 1995. Immunogenic properties of rabbit haemorrhagic disease virus structural protein VP60 expressed by a recombinant baculovirus: an effect vaccine. Virus Res. 39 (2-3): 119-128. McCance, KL, Huether, SE 1990: Pathophysiology: Clinical concepts of disease processes. St. Louis, MO: Mosby. 339p. Meyer, D. J., Coles, E. H. and Rich, L. J. 1992. Urinary tract test abnormalities. pp. 71-81. In: Veterinary Laboratory Medicine: Interpretation and Diagnosis (Mills, L. ed.), W. B. Saunders Company, Philadephia. Meyer, D. J., Coles, E. H. and Rich, L. J. 1992. Hepatic test abnormalities. In: Veterinary laboratory Medicine: Interpretation and Diagnosis. Harcourt Brace Jovanovich, Inc., 55-70. Meyers G., Wirblich C. and Thiel H. J. 1991a. Genomic and subgenomic RNAs of rabbit haemorrhagic disease virus are both protein-linked and packaged into particles. Virology, 184, 677-686. Meyers G., Wirblich C. and Thiel H. J. 1991b. Rabbit haemorrhagic disease virus - molecular cloning and nucleotide sequencing of a calicivirus genome. Virology, 184, 664-676. Meyers, G., Christoph, W., Thiel, H. J. and Thumfart, J. O. 2000. Rabbit hemorrhagic disease virus: Genome organization and polyprotein processing of a Calicivirus studied after transient expression of cDNA constructs. Virology 276: 349-363. Mims, C. A. 1989. The pathogenetic basis of viral tropism. Am. J. Pathol. 135: 447-455. Mizoguchi, T., Itou, K. I. and Sakurai, M. 2003. Hemagglutination and antigenic comparison of rabbit hemorrhagic disease virus. J. Vet. Med. Sci. 65: 95-97. Mori, W., Machinami, R., Shiga, J., Taguchi, T., Tanaka, K., Fukusato, T., Hasegawa, A., Aoki, N., Narita, T. and Kikuchi, F. 1984. A pathological study of fulminant hepatic disease. Acta Pathol. Jpn. 34: 727-742. Moussa, A., Chasey, D., Lavazza, A., Capucci, L., Smid, B., Meyers, G., Rossi, C., Thiel, H. J., Vlasak, B., Ronsholt, L., Nowotny, N., McCullough, K. and Gravier-Widen, D. 1992. Haemorrhagic disease of lagomorphs: Evidence for a calicivirus. Vet. Microbiol. 33: 375-381. Munro, R. K. and Williams, R. T. 1994. Rabbit hemorrhagic disease: issues in assessment for biological control. Canberra, Australia, Bureau of Resources Sciences, Australian Government Publishing Service. 116-121. Mutze, G., Cooke, B. and Alexander, P. 1998. The initial impact of rabbit hemorrhagic disease on European rabbit populations in South Australia. J Wildlife Disease. 34(2): 221-227. Nardelli, S., Agnoletti, F., Costantini, F. and Parpajola, R. 1996. Diagnosis of rabbit hemorrhagic disease (RHD) and European brown hare syndrome (EBHS) by indirect sandwith polyclonal ELISA. J. Vet. Med. B 43: 393-400. O’Keefe, J. S., Tempero, J. E., Motha, M. X., Hansen, M. F. and Atkinsona, P. H. 1999. Serology of rabbit haemorrhagic disease virus in wild rabbits before and after release of the virus in New Zealand. Vet. Microbiol. 31: 29-40. Ohlinger, V. F., Haas, B. and Thiel, H. J. 1993. Rabbit haemorrhagic disease (RHD): Characterization of the causative calicivirus. Veterinary Research. 24: 103-116. Ohlinger, V. F., Haas, B., Meyers, G., Weiland, F. and Thiel, H. J. 1990. Identification and characterization of the virus causing rabbit haemorrhagic disease. J. Virol. 64: 3331-3336. Panann-Duran, J., Bastons, M., Rodriguez, M. J., Climent, I., Cortes, E., Vela, C. and Casal, I. 1996. Oral immunization of rabbits with V 60 particles confers protection against rabbit hemorrhagic disease. Arch. Virol. 141(8): 1423-1436. Park J. H., Lee, Y. S. and Itakura, C. 1995. Pathogenesis of acute necrotic hepatitis in rabbit hemorrhagic disease. Lab. Anim. Sci. 45: 445-448. Park, J. H. and Itakura C. 1992a. Detection of rabbit haemorrhagic disease virus antigen in tissues by immunohistochemistry. Research in Veterinary Science. 52: 299-306. Park, J. H., Ochiai, K. and Itakura, C. 1992b. Detection of rabbit haemorrhagic disease virus particles in the rabbit liver tissues. J. Comp. Path. 107: 329-340. Park, J. H., Ochiai, K. and Itakura, C. 1993. Aetiology of rabbit haemorrhagic disease in China. Veterinary Record. 133: 67-69. Parkers, J. P., Norbury, G. L., Heyward, R. P., and Sullivan, G. 2002. Epidemiology of rabbit hemorrhagic disease (RHD) in the South Island, New Zealand, 1997. Wildlife Research. 29: 543-555. Philbey, A. W., Kirkland, P. D. and Saunders, G. R. 2005. Assessment of antibodies to rabbit haemorrhagic disease virus in fox serum as an indicator of infection in sympatric rabbit populations. Aust. Vet. J. 83(1-2): 97-100. Plassiart, G., Guelfi, J. F., Ganiere, J. P., Wang, B., Andre, F. G. and Wyers, M. 1992. Hematological parameters and visceral lesions relationships in rabbit viral hemorrhageic disease. J. Vet. Med. Ser. B 39: 443-453. Ren, J., Wang, L., Chen, Z., Ma, Z. M., Zhu, H. G., Yang, D. L., Li, X. Y., Wang, B. I., Fei, J., Wang, Z. G. and Wen, Y. M. 2006 Gene expression profile of transgenic mouse kidney reveals pathogenesis of hepatitis B virus associated nephropathy. J. Med. Virol. 78: 551-560. Ros Bacunana, C., Nowotny, N. and Belak, S. 1997. Detection and differentiation of rabbit hemorrhagic disease and European brown hare syndrome viruses by amplification of VP60 genomic sequences from fresh and fixed tissue specimens. J. Clin. Microbiol. 35(10): 2492-2495. Sanchez-Campos, S., Alvarez, M., Culebras, J. M., Gonzalez-Gallego, J. and Tunon, M. J. 2004. Pathogenic molecular mechanisms in an animal model of fulminant hepatic failure: rabbit hemorrhagic viral disease. J. Lab. Clin. Med. 144: 215-222. Sanson, R. L., Brooks, H. V., and Horner, G. W. 2000. An epidemiological study of the spread of rabbit hemorrhagic disease virus among previously non-exposed rabbit populations in the North Island of New Zealand. New Zealand Vet. J. 48: 105-110. Sauar, J., Blomhoff, J. P., and Gjone, E., 1976. Triglyceride lipases in acute hepatitis. Clin. Chim. Acta. 71, 403-411. Schirrmeier, H., Reimann, I., Köllner, B. and Granzow, H. 1999. Pathogenic, antigenic and molecular properties of rabbit haemorrhagic disease virus (RHDV) isolated from vaccinated rabbits: detection and characterization of antigenic variants. Arch. Virol., 144: 719-735. Shien, J. H., Shieh, H. K. and Lee, L. H. 1998. Characterization of rabbit hemorrhagic disease field isolates in Taiwan. J. Viol. Med. 71: 27-33. Shien, J. H., Shieh, H. K. and Lee, L. H. 2000. Experimental infections of rabbits with rabbit hemorrhagic disease virus monitored by polymerase chain reaction. Res. Vet. Sci. 68: 255-259. Smid, B., Valicek, L., Rodak, L., Stepanek, J. and Jurak, E. 1991. Rabbit haemorrhagic disease: an investigation of some properties of the virus and evaluation of an inactivated vaccine. Vet. Microbiol. 26: 77-85. Songsivilai, S., Dharakui, T. and Senawong, S. 1995. Hepatitis B- and hepatitis C-associated hepatocellular carcinoma: evaluation of alpha-fetoprotein as a diagnostic marker. Asian Pac. J. Allergy Immunol. 13: 167-171. Stoerckle-Berger, N., Keller-Berger, B., Ackermann, M.and Ehrensperger F. 1992. Immunohistological diagnosis of rabbit haemorrhagic disease (RHD). J. Vet. Med. [B], 39: 237-245. Sun, J. L., Hu, Y. L., Wang, D. Y., Zhang, B. K. And Liu, J. G. 2006. Immunologic enhancement of compound Chinese herbal medicines. Vaccine. 24(13): 2343-2348. Thompson, J. and Clark, G. 1997 Rabbit calicivirus now established in New Zealand. Surveillance. 24: 5-6. Torres J.M., Ramirez M.A., Morales M., Barcena J., Vazquez B., Espuna E., Pages Mante, A. and Sanchez-Vizcaino, J. M. 2000. Safety evaluation of a recombinant myxoma-RHDV virus inducing horizontal trasmissible protection against myxomatosis and rabbit heamorrhagic disease. Vaccine 19: 174-182. Treseler, K. M. 1995. Clinical Laboratory and Diagnostic Tests: Significance and nursing implications. 3rd. E. Norwalk, CT: Appleton & Lange. 71-75pp and 480pp. Tunon, M. J., Sonia, S. C., Javier, G. F., Marcelino, A., Francisco, J. and Javier, G. G. 2003. Rabbit hemorrhagic viral disease: characterization of a new animal model of fulminant liver failure. J. Lab. Clin. Med. 141: 272-278. Vergani, C., Trovato, G., Delu, A., Pietrogrande, M., and Dioguardi, N. 1978. Serum total lipids, lipoprotein cholesterol, and apolipoprotein A in acute viral hepatitis and chronic liver disease. J. Clin. Pathol. 31: 772-778. Villafuerte, R., Calvete, C., Gortazar, C. and Moreno, S. 1994. First Epizootic of rabbit hemorrhagic disease in free living populations of Oryctolagus cuniculus at Donana National Park, Spain. J. Wildlife Diseases 30(2): 176-179. Weisbroth, S. H., Flatt, R. E. and Kraus, A. L. 1974. Anatomy, physiology, and biochemistry of the rabbit. In: The Biology of the Laboratory Rabbit. Academic Press Inc., San Diego. pp. 49-72. Wirblich, C., Meyers, G., Ohlinger, V. F., Capucci, L., Eskens, U., Haas, B. and Thiel, H.-J. 1994. European brown hare syndrome virus: relationship to rabbit hemorrhagic disease virus and other caliciviruses. J. Virol. 68: 5164-5173. Xu, E. J. and Chen, W. X. 1989. Viral hemorrhagic disease in rabbits: a review. Vet. Res. Commun. 13: 205-212. Young, S. L., Wilson, M., Wilson, S., Beagley, K. W., Ward, V. and Baird, M. A. 2006. Transcutaneous vaccination with virus-like particles. Vaccine 24(26): 5406-5412.||摘要:||
兔出血熱病(rabbit hemorrhagic disease; RHD)屬於必須通報世界動物衛生組織的兔科疾病，本病最早於1984年在中國大陸爆發，隨後橫掃歐洲、中東及亞洲。台灣於1994年首次發生RHD疫情，當時由呂榮修博士藉由血清學檢查證實，其後數年內RHD重創整個台灣的養兔事業與生物製劑業。本試驗之研究目的是藉由詳細的血清生化變化與病理學檢查來了解與釐清兔出血熱病毒之致病機轉，同時找出最適合做為早期篩檢猛爆型肝炎病兔與病程監控之指標，供做後續研究之依據。
兔出血熱病主要引起急性致死的壞死性病毒性肝炎，2月齡以上的成兔於染病後36-72小時間即暴斃，其致死率高達85%。在第一個試驗中，15週齡的紐西蘭白兔經接種兔出血熱病毒(rabbit hemorrhagic disease virus; RHDV)後，血清中天門冬酸鹽轉氨酶(AST)、氨基丙酸轉氨酶(ALT)、乳酸鹽脫氫酶 (LDH)、加瑪麩氨基酸轉換酶(r-GT)及鹼磷酶(ALP)的上升均達極顯著水準(p<0.0001)。在配對血清(paired serum sampling)檢測方面，接種18小時後立即分別有95%、89%與61%的接種兔呈現血清中AST、ALT與LDH等漏出性酵素增加的現象。與平均正常值比較時發現，接種18小時後，血清中AST為正常值之16倍，ALT為正常值之4倍，而LDH則為正常值之1.3倍；而接種後42小時的值達最高點，其中AST為正常值之47倍，ALT為正常值之11倍，而LDH則為正常值之8倍。
不同於前述3種酵素，ALP一直到接種24小時後，才開始逐漸上升，顯著上升則在接種後第30小時開始出現。最大值(691.92 IU/L)出現在接種後第42小時，是平均正常值的5倍。r-GT的變化則更遲且更緩慢，顯著性的上升一直到接種後第36小時才出現；直到接種後第42小時，才有83%的接種兔出現血清r-GT檢測值高於正常值上限(14.4 IU/L)的情形，此時血清中之檢測值達其最高平均值(59.85±34.02IU/L)，為平均正常值的7.8倍。而r-GT/ALT比，於接種後30小時內先呈下降趨勢，待36小時起方呈增加現象，但試驗期間所有的r-GT/ALT比值均低於正常值；這顯示接種後42小時內，血清中ALT與r-GT的增加主因肝細胞的損傷而非膽道阻塞所致。對死亡RHDV接種兔的肝臟進行病理學檢查發現，其病理變化隨著肝血清酵素的增加而加劇。這種種結果顯示血清中肝細胞酵素之持續上升代表RHDV的感染導致快速且嚴重之肝損害，而血清中呈對數性上升的AST及ALT則為預測RHD趨向猛爆性的最佳指標。
在測定血清中腎功能與電解質等相關成分的試驗中，血清中尿素氮(BUN)、肌酸酐(CREA)及鈉(Na+)的上升與低血糖的發展均達極顯著差異(p<0.0001)；而鉀(K+)的上升亦達顯著差異(p<0.05)。有5隻兔子於血糖低於20 mg/dl後的2小時內死亡。血清中BUN與CREA的値與正常値相比較，其差異顯著性(p<0.05 vs. baseline)分別出現於接種後第36與42小時。雖然死亡兔子的BUN與CREA均較平均正常値高，但是3隻於58小時後犧牲的兔子其犧牲前最後一次採血之血清BUN與CREA之平均値均較前者更高。同樣的情形也出現在平均滲透壓(osmolality)，死亡兔子的平均值顯著(p<0.05)低於存活超過58小時者。RHDV對腎功能的傷害由接種後36小時才開始逐漸上揚的BUN與CREA的表現可知，其功能不足的情形隨著病情的惡化逐漸加重；而血清中電解質的顯著變化，使胞外液滲透壓上升，擾亂體液的流動方向，進而導致細胞恆定的破壞。因此逃過急性猛爆期後的病兔，其腎功能的下降與電解質的不平衡仍是這些倖存者莫大的威脅。
隨著血清中AST、ALT和r-GT的顯著上升(p<0.0001)，三酸酸甘油脂(triglyceride; TG)與膽固醇(cholesterol; CHOL)的升高也達顯著水準（ptriglyceride <0.0001，p cholesterol =0.0003），其中又以三酸酸甘油脂的上升速率呈對數性最為顯著。RHDV接種30小時後發生的高血脂(hyperlipidemia)現象顯示，RHDV的感染會損害脂肪代謝反應的運作。
RHDV接種後24小時起，血清甲型胎兒蛋白(Alpha-fetoprotein；AFP)的濃度也隨著AST、ALT、r-GT和ALP的顯著上升而逐漸攀升(P AFP=0.0082)。接種RHDV而死亡的兔子，死前最後一次AFP値的平均值，高達4.22± 1.61 ng/ml (n=6)。相關性統計分析（correlation analysis）的結果顯示AFP的變化與ALP變化的相關性高於r-GT，但與AST和ALT的變化的相關性卻未達顯著水準。這樣的結果顯示造成AFP上升的主因是隨著肝細胞漏出性酵素上升後，肝細胞嚴重壞死後所釋出。
Rabbit hemorrhagic disease (RHD), a notifiable disease for OIE, was first reported in 1984 in China and dispersed into Europe, the Middle East and Asia. In Taiwan, RHD was first reported by Dr. Y. S. Lu by serological tests in 1994 and severely damaged the rabbit-raising industry and the bio-products industry in the following years. The purpose of this study is to use serum biochemistry tests along with histopathological examination to construct the pathogenesis of rabbit hemorrhagic disease virus (RHDV) as a useful index for medical treatment in fulminant viral hepatitis in human and animals.
RHD infection has been characterized as an acute fatal necrotic viral hepatitis in up to 85% adult (older than 2 months) rabbits died within 36 to 72 hours after infection. In the first study, after RHDV inoculation, highly significant elevations in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), r-glutamyltransferase (r-GT) and alkaline phosphatase (ALP) (p<0.0001) were noted. In comparison with baseline values (pair serum comparison), rabbits with leakage enzymes elevated immediately at 18 HPI were 95%, 89% and 61% for AST, ALT and LDH, respectively. In comparisons with the means of baseline, the changes were about 16 times, 4 times and 1.3 times at 18 HPI for AST, ALT and LDH, respectively. The maximal values appeared at 42HPI, there were 47 times, 11 times and 8 times for AST, ALT and LDH, respectively.
Differently from parameters above, the ALP was not elevated until 24HPI. Significant increasing observed later at 30 HPI. The means peaked at 42 HPI with a value of 691.92 IU/ L which was about 5 times of the baseline mean. The elevation of r-GT was even more gradual and later by time proceeded, it significantly increased at 36 HPI in comparison with baseline value. The frequency distribution revealed that only 83% tested samples had values over the upper limit (14.4 IU/L) at 42HPI. The peak mean appeared at 42 HPI (59.8534.02IU/L) which was 7.8 times of the base line mean. The r-GT /ALT ratios tended to decreasing from baseline to 30HPI and then increasing from 36HPI to 42HPI, but all mean ratios after infection were lower than baseline one. This indicated that the increase of serum ALT and r-GT were mainly from hepatocellular disease instead of biliary tract disease in the first 42 hours. Histopathological findings of the liver from the dead rabbits correlated well chronologically with the release of the liver enzymes into the serum. Our results suggested that profound changes in serum liver enzymes implicated the damage in liver is fast and severe, and the exponential elevations in AST and ALT would be a strong prediction of the fulminant consequence in RHD.
The investigation on the damage of renal function and electrolyte balance found after virus inoculation, serum blood urea nitrogen (BUN), creatinine (CREA) and sodium (Na+) were elevated to a highly significant level (p<0.0001), whereas serum potassium (K+) was moderately elevated to a significant level (p<0.05). Hypoglycemia developed highly significantly (p<0.0001). The rabbits would die within 2 hr when the glucose level was lower than 20 mg/dl (in 5 rabbits). Significant elevation in serum BUN and CREA (p<0.05 vs. baseline) appeared at 30 HPI and 36 HPI, respectively. Although the means of BUN and CREA were higher than the baseline in rabbits prior to death, the surviving 3 rabbits (survived over 58 HPI) had even higher means prior to sacrifice. The mean osmolality value of surviving rabbits was higher than the dead ones. The dying rabbits had significantly lower values than the surviving ones. Renal insufficiency progressed from 30 hr, as indicated by the increases in BUN and CREA; significant changes in electrolytes resulting in the increased osmolality of extracellular fluid that induced flow disturbance which consequently destroy the homeostasis in cells. Therefore, the later impairments in renal function and electrolyte balance following liver injury might be an important threat for rabbits which might have survived from acute fulminant hepatitis in RHD.
On the study of lipid metabolism, hyperlipidemia was observed (p triglyceride <0.0001, p cholesterol =0.0003) along with significant increases in serum AST, ALT and r-GT (p<0.0001) after RHDV inoculation. An exponential increase in serum triglyceride was also seen. Thus, the presence of hyperlipidemia (from 30 hours post-inoculation) in the infected rabbits points to impairment in lipid metabolism.
Serum alpha-fetoprotein (AFP) elevated significantly (p=0.0082) from 24 HPI together with significantly elevated AST, ALT, r-GT and ALP after RHDV inoculation. Rabbits that died tend to have high AFP values prior to death, the mean value being 4.22 1.61 ng/ml (n=6). By correlation analysis, AFP significantly correlated more strongly to ALP than r-GT, but insignificantly with AST and ALT suggested that the elevation in AFP was later released from severer hepatic necrosis following the leakage of cytoplasmic enzymes.
In conclusion, the results above showed that RHDV mainly caused massively necrosis in liver first. The severe hypoglycemia caused the death of the rabbits in the acute phases. Following the progression of the disease, renal function, electrolyte balance and lipid metabolism were all impaired and threatened the life of the survivals. Although the AFP was elevated later, the lack of normal hepatocytes for regeneration could not save the infected rabbits from systemic failures. Fulminant liver disease is regarded as a group of systemic diseases with the main focus of illness in the liver. Therefore, the measurements of renal function, electrolytes balance, serum glucose level and lipid metabolism as well as liver functional parameters for monitoring the progression in a fulminant viral hepatitis as index for medical treatment are necessary.
|Appears in Collections:||獸醫學系所|
Show full item record
TAIR Related Article
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.