培哚普利和氯沙坦对肝纤维化组织TLR4表达的影响

目的观察大鼠正常肝脏和肝纤维化(HF)组织Toll样受体4(TLR4)表达差异及培哚普利(Pe)和氯沙坦(Lo)对其的影响。方法 Wistar雄性大鼠随机分为假手术组(Sham组)、胆总管结扎术(BDL组)、Pe 14 d和30 d及Lo 14d和30d组,6只/组。BDL组和治疗组均通过BDL制备大鼠HF模型。予Pe(2 mg/kg)和Lo(50 mg/kg)灌胃,1次/dc 14 d和30 d后分别应用Westernblotting检测肝脏TLR4水平。结果 BDL 14 d组大鼠肝脏TLR4为Sham组的(6.53±1.11)倍(P<0.05);Pe 14 d组和Lo 14 d组TLR4分别下降到Sham组的(1.71±0.41)倍(P>0.05)和(0.95±0.38)倍(P>0.05)。Pe 30 d组和Lo 30 d组大鼠肝脏TLR4分别回升为Sham组的(6.51±0.87)倍(P<0.05)和(5.64±0.87)倍(P<0.05)。结论大鼠HF后肝脏TLR4水平上升,Pe和Lo可降低实验性HF组织的TLR4水平,但长期服用其抑制TLR4的作用减弱。

Perindopril and losartan attenuate intrahepatic Toll-like receptor 4 protein expression in rats with bile duct ligation-induced hepatic fibrosis

Objective To investigate the expression of Toll-like receptor 4(TLR4) in the liver tissue of rats with bile duct ligation (BDL)-induced hepatic fibrosis and evaluate the inhibitory effects of perindopril and losartan on TLR4 expression.Methods Male Wistar Rats were randomly divided into sham-operated group(n=6),BDL group,perindopril treatment group(2 mg/kg) and losartan treatment group(50 mg/kg)(n=12).Perindopril and losartan groups were further divided into two subgroups for corresponding treatments by gastric lavage once daily for 14 and 30 days.The protein level of TLR4 in the liver tissue was examined by Western blotting.Results In 14-day BDL group,the protein level of TLR4 significantly increased to 6.53±1.11 folds of that in the sham group(P<0.05),and was lowered significantly to 1.71±0.41 folds and 0.95±0.38 folds following perindopril and losartan treatments for 14 days.TLR4 expression significantly increased to 6.51±0.87 folds and 5.64±0.87 folds of that of the sham group in perindopril and losartan groups after the 30-day treatments(P<0.05).Conclusion TLR4 expression is up-regulated in the liver of rats with BDL-induced hepatic fibrosis,and can be lowered by perindopril and losartan treatmemts for 14 days.