生理剂量的雌激素对雌、雄性大鼠肝纤维化形成的影响

The effects of physiological dose of β-Est on rat liver fibrosis in both sexes

目的探讨生理剂量的β-Est对雌、雄性大鼠肝纤维化形成的影响。方法采用皮下注射CCl4制作大鼠肝纤维化模型,观察β-Est(0.02 mg.kg-1.d-1)对完整或去势雌、雄性大鼠肝纤维化形成的影响。6周后收集肝组织和血清标本,以标准酶法、ELISA、RIA分别测定血清肝功能、ECM及性激素水平;VG染色观察肝脏组织学改变,结合图像分析计算胶原面积。结果在相同剂量CCl4作用下雄性大鼠肝纤维化反应较雌性大鼠强烈;补充生理剂量β-Est能改善雌性、去势肝纤维化大鼠肝功能,降低其ECM分泌及肝组织纤维化程度;去势加重雌性大鼠肝纤维化反应;而生理剂量β-Est或去势对雄性大鼠肝纤维化形成无影响。结论内源性雌激素能抑制CCl4诱导的大鼠肝纤维化,而不同性别对雌激素反应各不相同,这可能是导致肝纤维化形成具有性别差异性的原因之一。

Objective To investigate the effects of physiological dose of β-Est on rat liver fibrosis in both sexes.Methods Liver fibrosis was induced by CCl4.The fibrosis-suppressive effect β-Est（0.02 mg·kg-1·d-1） was evaluated in intact or gonadectomy rat model in both sexes.At the 6th week after the treatment,all rats were sacrificed.The serum levels of AST,ALT and ALB were determined by standard enzymatic methods;the serum levels of HA,PCⅢ,CⅣ,LN were determined by ELISA;serum levels of E2,T were determined by RIA;the degrees of fibrosis in the livers were determined by VG stain.Results The fibrotic response of the male rat liver after CCl4 treatment was significantly stronger than that of the female rat liver;β-Est treatment at a physiological dose could improve the serum levels of AST,ALT and ALB,reduce ECM secretion,and suppress hepatic collagen deposition in female and gonadectomy rat model significantly;ovariectomy in the female rat model enhanced the fibrogenic effect;Neither gonadectomy nor β-Est had fibrosuppressive effects in the rat male model as judged by the same parameters.Conclusion These findings suggest that endogenous estrogen can suppress the liver fibrosis induced by CCl4,but there is a sexually dimorphic response pattern of the injured liver to estrogen,and this may be the cause of sexual difference in liver fibrosis.