肝纤维化大鼠性激素的变化及己烯雌酚对大鼠肝纤维化影响的实验研究

SUPPRESSIVE EFFECTS OF ESTRADIOL ON PIG SERUM-INDUCED FIBROSIS OF THE LIVER AND THE RELATIONSHIP BETWEEN THE LEVELS OF SERUM SEXUAL HORMONES AND CIRRHOSIS IN RATS

目的 :探讨肝纤维化大鼠性激素的变化及己烯雌酚对大鼠肝纤维化的影响 ,以期对肝纤维化的治疗提供一种新的途径。方法 :Wistar大鼠按性别分为两大组 ,各大组随机分为空白对照组 ,肝纤维化模型组 ,己烯雌酚 (DES)干预组。对照组 :腹腔注射生理盐水 (NS) 0 .5ml/只 /次 ,2次 /周 ,共 12周 ;模型组 :腹腔注射猪血清(PS) 0 .5ml/只 /次 ,2次 /周 ,共 12周 ;干预组 :腹腔注射猪血清 0 .5ml/只 /次 ,2次 /周 ,共 12周 ,并于第 9周始腹腔注射己烯雌酚 1.2mg/kg/次 ,2次 /周 ,共 4周。于 12周末处死全部实验动物 ,留血清采用放射免疫法检测各组大鼠血清性激素 (雌二醇、睾酮、孕酮 )水平及透明质酸 (HA)、Ⅲ型前胶原 (PCⅢ )、Ⅳ型胶原 (Ⅳ -c)、层粘连蛋白 (LN)等纤维化指标 ;取肝组织进行HE染色、Masson染色及Ⅰ、Ⅲ型胶原的免疫组化染色 ,对肝纤维化进行病理分期 ,对免疫组化结果进行半定量分析。结果 :肝纤维化模型组的纤维化程度明显较空白对照组为重 (P <0 .0 5 ) ,DES干预组的纤维化程度与肝纤维化模型组比较明显减轻 (P <0 .0 5 )。此外 ,肝纤维化模型组的雌二醇 (E2 )、睾酮 (T)浓度较空白对照组明显下降 (P <0 .0 5 ) ,孕酮 (P)的浓度无明显改变 (P >0 .0 5 )。E2 、T、P三者与肝纤维化指标 (Ⅰ。

Objective:To analyze the fibrosuppressive role of estradiol and the relationship between the levels of serum sexual hormones and cirrhosis.Methods:Male and female Wistar rats weighing 120～150g were used in this experiment. Rats of the same sex were divided into three groups respectively. The pig serum (PS) models were given intraperitoneal injections of PS (0.5ml) twice per week for 12 weeks, the control rats received biweekly injections of normal saline (0.5ml) for 12 weeks, and the diethylstilbestrol (DES) models received intraperitoneal injections of DES (1.2mg/kg) biweekly during the last 4 weeks of PS treatment. All animals were killed after 12 weeks, blood samples were collected from the heart ,and used for radioimmunoassay of estradiol (E 2) ,testosterone (T) , progestin (P),HA, PC Ⅲ, Ⅳ-c and LN .Liver tissue specimens were used for light microscopy and immunohistochemistry using Type Ⅰ and Ⅲ collagen antibodies.Results:In the PS models, the treatment with DES resulted in a suppression of hepatic fibrosis with reduced collagen contents. The serum levels of E 2 and T decreased in PS models compared to the controls, and P levels had no significant difference among the three groups of the same sex. The correlation coefficients between the levels of sexual hormones and cirrhosis were higher than the significance level.Conclusion:Estradiol suppresses the induction of hepatic fibrosis and there is no linear correlation between the levels of sexual hormones and cirrhosis.