摘要
目的研究血管紧张素Ⅰ型(AT1)受体阻断剂对免疫性大鼠肝纤维化的影响。方法采用猪血清诱导建立肝纤维化模型,以大剂量和普通剂量缬沙坦干预,观察肝组织纤维化程度、胶原表达变化;免疫组化染色观察α平滑肌肌动蛋白(αSMA)、转化生长因子β1(TGFβ1)及核因子(NF)κBp65表达情况。结果与模型组比较,治疗组胶原面积显著减少,具有剂量依赖性(P<0.05),纤维化程度也明显改善;模型组αSMA、TGFβ1、NFκBp65表达增强(P<0.05),缬沙坦治疗后,都有不同程度的减弱,模型组和大剂量组αSMA分别为19.68±1.28和8.66±1.72,TGFβ1分别为22.36±4.77和9.95±2.28,NFκBp65分别为30.31±4.16和19.80±1.96(均为面密度值,P<0.05)。结论缬沙坦能明显抑制猪血清诱导的大鼠肝纤维化发生,可能与抑制肝星状细胞活化、增殖,降低TGFβ、NFκBp65等表达有关。
Objective To assess the effects of angiotensin Ⅱ type 1 receptor blockade on preventing immune induced hepatic fibrosis by pig serum injection in rats, and study its mechanisms.Methods Experimental models were produced by repeated intraabdominal injection of pig serum(twice a week for 8 weeks).After treating with valsartan for 8 weeks (15 mg/kg, 30 mg/kg),all rats were sacrificed. Liver fibrosis was assessed directly by hepatic morphometric analysis, the expression of α-smooth muscle actin (α-SMA), transforming growth factor-beta 1(TGF-β 1),nuclear factor-NFκB (NFκB p65) in liver tissue were determined by immunohistochemical techniques. Results Compared with model group, the fibrosis development in valsartan treatment group were lightened significantly (P<0.05), the area of collagen was markedly decreased (P<0.05),and such inhibition was dose-dependent. The expression of α-SMA, TGF-β 1, NFκB p65 in liver tissue were markedly increased in model groups ,but reduced significantly in valsartan treatment group (P<0.05).Conclusion Angiotensin Ⅱ type 1 receptor blockade significantly delayed the progression of pig serum-induced liver fibrosis in rats with a dose-dependent manner, and may be related to the reduction of activation and proliferation of hepatic stellate cells and decrement of the expression of TGF-β 1 ,NFκB p65.
出处
《肝脏》
2005年第2期110-112,共3页
Chinese Hepatology
