【摘要】 目的:观察血管紧张素转换酶抑制剂（angiotensin-converting enzyme inhibitor, ACEI）类药物卡托普利对肝纤维化大鼠肝功能的调节作用,探究其抗肝纤维化的分子机制。方法:采用四氯化碳（CCl₄）诱导肝纤维化大鼠动物模型,并应用卡托普利进行治疗,于20周末采集大鼠肝组织及腹主动脉血。观察肝脏组织学变化,采用ELISA法检测大鼠血清谷草转氨酶（aspartate aminotransferase, AST）和谷丙转氨酶（alanine aminotransferase, ALT）水平;分别采用RT-PCR法和免疫组化法检测大鼠肝组织中Ⅰ型胶原蛋白（collagenⅠ）和α-平滑肌肌动蛋白（alpha-smooth muscle actin,α-SMA）的mRNA和蛋白表达变化。结果:（1）模型组大鼠血清AST、ALT与对照组相比升高（P=0.000）,与模型组比较,ACEI高、中剂量组血清ALT表达水平均降低（P=0.000;P=0.010）,ACEI高剂量组血清AST表达水平降低（P=0.032）。（2）模型组大鼠肝组织Collagen-Ⅰ和α-SMA mRNA和蛋白表达较对照组均升高（P=0.000）,与模型组比较,ACEI各治疗组上述指标表达水平均降低（P=0.000）。结论:卡托普利能够改善肝纤维化大鼠的肝功能,缓解肝纤维化程度,该作用与其抑制HSC的激活并下调肝组织Collagen I和α-SMA的表达水平有关。更多还原

【Abstract】 Objective:To observe the regulation of angiotensin-converting enzyme inhibitor(ACEI) drug captopril on liver function in rats with liver fibrosis, and explore its anti-fibrotic mechanism. Methods: CCl4 was used to induce liver fibrosis in a rat model, and captopril was used for experimental treatment, with rat liver tissue and abdominal aortic blood collected at the end of the 20 th week. Liver histological changes were observed; ELISA method was used to detect rat serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) levels; RT-PCR and immunohistochemical methods were used respectively to detect the mRNA and protein expression of Collagen Ⅰ and α-smooth muscle actin(α-SMA) in rat liver tissue. Results:(1) Serum AST and ALT in the model group were significantly increased compared with those of the control group(P=0.000). Compared with those of the model group, the serum ALT expression levels of the ACEI in high and medium dose groups were significantly reduced(P=0.000; P=0.010), and the expression level of serum AST in the high-dose ACEI group was significantly reduced(P=0.032).(2) The expression of proteins and mRNA of Collagen Ⅰ and α-SMA in the model group were significantly higher than those in the control group(P=0.000). Compared with the model group, the expression levels of the above indicators in each treatment group of ACEI were significantly reduced(P=0.000). Conclusion: Captopril can improve the liver function and alleviate the degree of liver fibrosis in rats with liver fibrosis, which may be related to its intervention in the activation of hepatic stellate cells to inhibit the expression of collagen Ⅰ and α-SMA.更多还原