三價鉻離子對以腎上腺刺激激素刺激之大鼠體內醣皮質固醇分泌的影響

Abstract

庫興氏症候群 (Cushing’s syndrome) 是由於慢性內源性或外源性醣皮質固醇過多造成。依照是否分泌過量腎上腺刺激激素，庫興氏症候群可分為腎上腺刺激激素依賴型及非腎上腺刺激激素依賴型，其中不論在人類及犬隻，腎上腺刺激激素依賴型為最常見的病因。三價鉻離子不只是動物體內不可或缺的元素，因具有多項有益處的生理功能，許多研究也探討鉻離子在臨床上的各種應用。根據許多研究報告，我們假設三價鉻離子藉由減少腎上腺醣皮質固醇的分泌，能緩和庫興氏症候群。本實驗將大鼠分為4組，給予安慰劑及生理食鹽水之大鼠為控制組，給予三價鉻離子及生理食鹽水之大鼠為鉻離子組，給予安慰劑及腎上腺刺激激素之大鼠為腎上腺刺激激素組，給予三價鉻離子及腎上腺刺激激素之大鼠為三價鉻離子及腎上腺刺激激素組，每天給予並持續28天後以人道方式將大鼠犧牲。每星期秤量各組大鼠體重，並測量第28天大鼠臟器重、血液醣皮質固醇、AST、ATL及ALP濃度，以及進行腎上腺及肝臟組織學檢查。結果顯示給予三價鉻離子於以腎上腺刺激激素刺激的大鼠，其血中醣皮質固醇、AST、ALT及ALP濃度較未給予鉻離子之以腎上腺刺激激素刺激的大鼠低。此外組織學檢查顯示在給予三價鉻離子於以腎上腺刺激激素刺激的大鼠，其腎上腺之束狀層及網狀層的細胞較未給予鉻離子之以腎上腺刺激激素刺激的大鼠小，細胞內之脂肪顆粒也較少，肝臟細胞內之空泡顆粒也較少。綜合以上結果，本實驗顯示給予三價鉻離子能減少以腎上腺刺激激素刺激的大鼠腎上腺分泌醣皮質固醇，並減緩因過量醣皮質固醇造成之肝臟損傷。

Cushing’s syndrome refers to the clinical manifestations induced by chronic exposure to excess endogenous or exogenous glucocorticoids. The cause of Cushing’s syndrome could be classified into adrenocorticotropic hormone (ACTH)-dependent and ACTH-independent, in which ACTH-dependent is the most common cause of spontaneous Cushing’s syndrome in humans and canines. Trivalent chromium (Cr3+) is not only an essential element for animals, it is also widely studied for its clinical use because of its variety of beneficial biological functions. Based on studies, we postulated that Cr3+ could be helpful on attenuating ACTH-dependent Cushing’s syndrome by decreasing the level of glucocorticoids. In this study, rats were randomly divided into four groups: (1) rats treatment of placebo and saline were taken as control group; (2) rats treatment of Cr3+ and saline were taken as Cr group; (3) rats treatment of placebo and ACTH were taken as ACTH group; (4) rats treatment of Cr3+ and ACTH were taken as ACTH with Cr group. After treatment for 28 days, all rats were sacrificed with humanism. The body weights every week , tissues weights, the levels of corticosterone, AST, ALT, ALP at the 28th day were measured, and histological examination of the adrenal gland and liver were observed. The results showed that Cr3+ supplementation in ACTH-stimulated rats decreased the levels of corticosterone, AST, ALT, ALP in comparison to ACTH-stimulated rats without Cr3+ supplementation. In addition, the histological examination showed the cells and lipid droplets in the zona fasciculata and the zona reticularis in the adrenal gland were smaller and fewer, and vacuoles in the hepatic cells were fewer in ACTH-stimulated rats with Cr3+ supplementation than that in ACTH-stimulated rats without Cr3+ supplementation. Taken up together, Cr3+ administration had an inhibitory effect on the secretion of corticosterone by adrenal gland in ACTH-stimulated rats and attenuated the hepatic damage caused by glucocorticoids excess.