论文部分内容阅读
目的 近期一系列的研究表明 ,组织纤维化的发生与组织局部RAS系统的激活有关 ,但局部RAS系统的活性与肝纤维化发生之间的关系仍然不明。本研究旨在阐述 :( 1)血管紧张素转化酶抑制剂和血管紧张素Ⅱ受体阻断剂对CCl4 诱导的实验性肝纤维化的疗效 ;( 2 )在肝纤维化发生过程中激活的肝星状细胞是否表达AT1受体。方法 将实验用SD大鼠随即分为对照组、模型组及 3组不同剂量的药物治疗组。除对照组和模型组外 ,三组治疗组即依钠普利组 ( 5mg/kg)、氯沙坦 ( 10mg/kg)、及依钠普利与氯沙坦联合治疗组。每天灌胃一次 ,共 6周。 6周后对肝组织标本和血清进行检测 ,肝纤维化程度判定依据胶原染色 ,利用计算机图象分析系统评价纤维化程度 ;AT1受体和α SMA表达采用免疫组化法检测。结果 与模型组相比 ,依钠普利、氯沙坦及联合用药组纤维化程度均有不同程度的改善 (P <0 .0 5) ,但三组药物治疗组间疗效并无差别 (P >0 .0 5) ;在正常大鼠AT1受体表达仅见于血管壁 ,但在纤维化大鼠AT1受体表达与纤维间隔的分布一致。体外培养的HSC在激活后同样表达AT1受体。结论 ( 1)血管紧张素转化酶抑制剂和AT1受体阻断剂均可抑制实验性肝纤维化的发生 ;( 2 )激活的HSC表达AT1受体 ;( 3)局部RAS的激活与肝纤维化的发生有关。
A series of recent studies have shown that the occurrence of tissue fibrosis is related to the activation of local RAS system, but the relationship between the activity of local RAS system and the occurrence of liver fibrosis is still unknown. The purpose of this study is to elucidate: (1) the efficacy of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on CCl4-induced experimental liver fibrosis; (2) activation of hepatic fibrosis Whether hepatic stellate cells express AT1 receptors. Methods The experimental SD rats were randomly divided into control group, model group and three groups of different doses of drug treatment group. Except the control group and the model group, the three treatment groups were enalapril (5mg / kg), losartan (10mg / kg), and enalapril combined with losartan. Gavage once daily for 6 weeks. Liver tissue samples and serum were detected after 6 weeks. The extent of hepatic fibrosis was evaluated by collagen staining and the degree of fibrosis was assessed by computer image analysis system. The expressions of AT1 receptor and α SMA were detected by immunohistochemistry. Results Compared with the model group, the degree of fibrosis in the groups of enalapril, losartan and combination therapy all improved to some extent (P <0.05), but there was no difference between the three groups > 0.05). AT1 receptor expression was found only in the vascular wall in normal rats, but the expression of AT1 receptor in fibrosis rats was consistent with the distribution of fibrotic fibers. In vitro cultured HSCs also express AT1 receptors after activation. Conclusions (1) Angiotensin-converting enzyme inhibitors and AT1 receptor blockers can inhibit the occurrence of experimental liver fibrosis; (2) activated HSC express AT1 receptor; (3) local activation of RAS and liver fibrosis Related to the occurrence of