大剂量螺内酯对大鼠肝纤维化进展及血管紧张素Ⅱ水平的影响

Influence of large-dose spironolactone on concentration of angiotensinⅡin rat hepatic fibrosis

目的 论证螺内酯的抗肝纤维化作用 ,动态观察其对大鼠肝纤维化进展中血管紧张素Ⅱ (AngⅡ )水平的影响。方法 90只SD大鼠随机分为 3组 :①正常对照组 (8只 ) :正常饮水饮食 ,皮下注射纯花生油 ;②模型组 (4 2只 ) :皮下注射 4 0 % (体积分数 )四氯化碳花生油溶液 ,辅以高脂、高胆固醇、低蛋白饮食 ;③螺内酯组 (4 0只 ) :造模方法同模型组 ,并以 10 0mg·g-1·d-1剂量的螺内酯灌胃。于 2、4、6、8周末 ,后两组分别处死一批动物 ,放免法测定其血清及肝匀浆中AngⅡ水平 ,取肝脏标本做HE和VG染色观察。结果 ①螺内酯组的一般状况较好 ,病理改变较模型组轻 ,胶原面积比减少 ,两者有显著差异 (P <0 .0 5 ) ;②螺内酯组和模型组大鼠血清及肝匀浆中AngⅡ水平均从第 2周开始较正常对照组显著升高 ;从第 4周开始 ,螺内酯组血清中AngⅡ水平较同期模型组显著升高 ,而肝匀浆中AngⅡ水平较同期模型组显著降低。结论 大剂量螺内酯可以部分抑制肝纤维化的进展 。

Objective To comfirm the anti-fibrotic effect of spironolactone and investigate the influence of spironolactone on concentration of angiotensinⅡ(AngⅡ) in rat hepatic fibrosis. Methods Ninety male Sprague-Dawly rats were randomly divided into three groups: control group (8 rats, subcutaneous injection of pure peanut oil, normal diet), model group (42 rats, subcutaneous injection of 40% CCl 4, 0.3 mL/100 g, twice a week, high cholesterol and low protein diet, 5% alcohol as the drink), and spironolactone group (40 rats, same dosage of CCl 4, high cholesterol and low protein diet, gastropufusion of spironolactone at the dose of 100 mg·kg -1·d -1). The animals were sacrificed at 2, 4, 6 and 8 weeks of administration. AngⅡ was assayed by radioimmunoassay. The liver tissues were stained, coded and examined. Results ① The general conditions of the rats of spironolactone group were better than those of the model group. The degree of fibrosis and the area of collagen in the liver of spironolactone group were less than those of the model group after the 4th week (P< 0.05). ② Levels of AngⅡrose gradually in the blood and liver homogenate of both groups from the 2nd week during the experiment. From the 4th week, levels of AngⅡin the blood of spironolactone group increased, but decreased in the liver homogenate compared with the model group. Conclusion Spironolactone can partly have a fibrogenesis-inhibiting effect on experimental liver fibrosis in rats. Its anti-fibrotic effects are probably related with the decrease in tissue AngⅡ level.