论文部分内容阅读
目的 组织纤维化的发生与局部肾素 血管紧张素系统 (renin angiotensinsystem ,RAS)激活有关。本研究 ,旨在通过观察血管紧张素转化酶抑制剂和血管紧张素 1型 (AT1)受体阻断剂对实验性肝纤维化的疗效 ,以期明确RAS在肝纤维化发病中的作用 ,并对AT1受体在肝内表达的特点及肝星状细胞 (HSC)是否表达该受体作初步探讨。方法 给予SD大鼠CCl4 的同时 ,给予血管紧张素转化酶抑制剂依那普利 (10mg·kg-1·d-1)和AT1受体阻断剂氯沙坦 (10mg·kg-1·d-1) ,共 6周。利用图像分析系统对肝纤维化程度进行评价。肝组织AT1受体表达采用免疫组化法检测。结果 依那普利和氯沙坦均可显著抑制大鼠肝纤维化的发生 (P <0 .0 5 ) ;联合应用相同剂量的依那普利和氯沙坦疗效与单独应用比较 ,差异无显著性 (P >0 .0 5 ) ,但可抑制氯沙坦治疗后血清血管紧张素Ⅱ水平的升高 (P<0 .0 5 )。正常大鼠AT1受体主要表达于血管壁 ,在肝纤维化 ,该受体分布与α 平滑肌肌动蛋白 (α SMA)表达纤维间隔分布一致。结论 肝纤维化的发生与RAS激活有关 ,RAS抑制剂具有良好的抗纤维化作用 ,但联合应用转化酶抑制剂和AT1受体阻断剂 ,并不增加其抗纤维化疗效。肝纤维化发生过程中 ,肝星状细胞功能的改变可能与其表达AT1受体有关。
Purpose The occurrence of tissue fibrosis is related to the activation of renin angiotensin system (RAS). This study aims to determine the role of RAS in the pathogenesis of liver fibrosis by observing the effects of angiotensin-converting enzyme inhibitors and angiotensin 1 type 1 (AT1) receptor blockers on experimental liver fibrosis The expression of AT1 receptor in the liver and hepatic stellate cells (HSC) whether the expression of the receptor for initial discussion. Methods CCl4 was given to SD rats, and the rats were given angiotensin converting enzyme inhibitor enalapril (10 mg · kg-1 · d-1) and losartan (10 mg · kg-1 · d -1) for 6 weeks. The degree of liver fibrosis was evaluated using an image analysis system. The expression of AT1 receptor in liver tissue was detected by immunohistochemistry. Results Both enalapril and losartan significantly inhibited the occurrence of hepatic fibrosis in rats (P <0.05). The combination of enalapril and losartan with the same dose showed no significant difference (P> 0.05), but it could inhibit the increase of serum angiotensin Ⅱ after losartan treatment (P <0.05). The normal rat AT1 receptor is mainly expressed in the vascular wall, and in the liver fibrosis, the distribution of this receptor is consistent with the distribution of α SMA smooth muscle fibers. Conclusions The occurrence of hepatic fibrosis is related to the activation of RAS. RAS inhibitor has a good antifibrotic effect. However, combination of invertase inhibitor and AT1 receptor antagonist does not increase its antifibrotic effect. In the process of liver fibrosis, the changes of hepatic stellate cells may be related to its expression of AT1 receptor.