目的：观察牛磺酸对四氯化碳所致大鼠肝硬化门静脉高压的影响，探讨其作用机制。方法采用四氯化碳复合法制备肝硬化门静脉高压大鼠模型。实验大鼠随机分为正常组、模型组、阳性药组和牛磺酸低、中、高剂量组，各给药组给予相应药物灌胃。治疗4周后，生化分析仪测定大鼠血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和总胆红素（TBIL）含量；ELISA测定大鼠血清肝纤4项[Ⅳ型胶原（CⅣ）、Ⅲ型前胶原（PCⅢ）、层粘连蛋白（LN）、透明质酸（HA）]含量以及肝组织羟脯氨酸（HYP）水平；血流动力学法测定大鼠门静脉压（PVP）、门静脉血流量（PVF）、平均动脉压（MAP）并测定心率（HR）；硝酸还原酶法测定一氧化氮（NO）含量，化学比色法测定内皮型一氧化氮合酶（eNOS）活性，放射免疫法测定环鸟苷酸（cGMP），紫外-可见分光光度计测定超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）活性和丙二醛（MDA）含量；HE 染色观察大鼠肝组织病理形态。结果与模型组比较，牛磺酸中、高剂量组大鼠血清ALT、AST和TBIL含量显著降低（P＜0.05，P＜0.01），CⅣ、PCⅢ、HA及HYP含量显著降低（P＜0.05， P＜0.01），牛磺酸高剂量组LN含量显著降低（P＜0.05）；牛磺酸中、高剂量组大鼠PVP、PVF显著降低（P＜0.05），牛磺酸高剂量组MAP显著升高且HR显著降低（P＜0.05）；牛磺酸中、高剂量组大鼠肝组织NO含量显著升高（P＜0.05，P＜0.01），牛磺酸高剂量组eNOS活性、cGMP含量显著升高（P＜0.05）；牛磺酸中、高剂量组大鼠肝组织SOD、GSH-Px活性显著升高且MDA含量显著降低（P＜0.05，P＜0.01）；牛磺酸各剂量组大鼠肝组织病变明显改善，其中牛磺酸高剂量组效果最为显著。结论牛磺酸对肝硬化门静脉高压大鼠具有抑制作用，其机制可能与牛磺酸保肝降酶，抑制氧化应激损伤，上调eNOS表达、提高NO含量，改善肝功能有关。%Objective To investigate the effects of taurine on rats with CCl4-induced portal hypertension; To discuss its mechanism of action. Methods CCl4 compound method was used to prepare portal hypertension rat models. Experimental rats were randomly divided into normal group, model group, positive medicine group and low-, medium- and high-dose taurine groups. Each medication group was given relevant medicine for gavage. After four-week treatment, biochemical analyzer was used to detect the contents of ALT, AST and TBIL;ELISA was used to detect the contents of CⅣ, PCⅢ, LN, HA and the level of HYP in serum;hemodynamic method was used to detect PVP, PVF, MAP and HR;nitrate reduction method was used to detect the contents of NO, chemical colorimetry was used to detect the activity of eNOS, hepatic tissue;the activity of SOD, GSH-Px and the content of MDA in hepatic tissue;HE staining was used to observe the histopathological changes of the hepatic tissue. Results Compared with the model group, the contents of ALT, AST and TBIL in serum in medium-and high-dose taurine groups decreased significantly (P<0.05, P<0.01);the contents of CⅣ, PCⅢ, HA and HYP in serum in medium-and high-dose taurine groups decreased significantly, and LN in high-dose taurine group decreased significantly (P<0.05, P<0.01);the PVP, PVF in medium- and high-dose taurine groups and the HR in high-dose taurine group decreased significantly (P<0.01), and the MAP in high-dose taurine group inecreased significantly (P<0.05); the content of NO in hepatic tissue of medium-and high-dose taurine groups increased significantly (P<0.05, P<0.01);the activity of eNOS and the content of cGMP in high-dose taurine group increased significantly (P<0.05); the activity of SOD, GSH-Px in hepatic tissue of medium- and high-dose taurine groups increased significantly and the content of MDA decreased significantly (P<0.05, P<0.01);the hepatic tissue histopath-ological changes of low-, medium-and high-dose taurine groups were significantly improved, especially the high-dose taurine group. Conclusion Taurine has inhibitory effects on rats with portal hypertension, which perhaps are related to its effects on enzyme activity inhibition and hepatic tissue protection, inhibiting the damage of oxidative stress, upregulating eNOS expression, enhancing the content of NO and improving liver function.
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