水飞蓟宾对CCl_4所致肝硬化门静脉高压大鼠的保护作用及其机制研究

目的:研究水飞蓟宾(Silibinin,SIL)对CCl_4所致肝硬化及门静脉高压大鼠的保护作用及其机制。方法:将120只SD大鼠随机分为正常对照组、模型对照组、SIL(25、50、100 mg/kg)治疗组和秋水仙碱(0.1 mg/kg)治疗组;采用四氯化碳复合法制备肝硬化门静脉高压大鼠模型;造模完成后灌胃给药,1次/d,疗程6周。测定肝功能指标:血清中转氨酶(ALT、AST)和总胆红素(TBI L)含量;HE染色法观察肝脏组织病理性形态学变化;测定血清中肝纤4项(CⅣ、PCⅢ、LN、HA)和肝脏组织中羟脯氨酸(HYP)水平;通过生理记录仪记录门静脉压(PVP)、门静脉血流量(PVF)、平均动脉压(MAP)并测定心率(HR);测定肝脏组织中一氧化氮(NO)、环鸟苷酸(cGMP)含量。结果:与模型组对照组比较,SIL(50、100 mg/kg)治疗组大鼠血清中ALT、AST、TBI L、CⅣ、PCⅢ、HA、HYP含量均显著降低(P0.05),PVP和PVF显著降低(P0.05),肝脏组织中NO含量显著升高(P0.01);SIL(100 mg/kg)治疗组大鼠血清中LN含量显著降低,MAP显著升高,HR显著降低,肝组织中cGMP含量显著升高,差异均具有统计学意义(P0.05);SIL各治疗组大鼠肝脏组织病理性形态学变化呈不同程度好转,其中以SIL 100 mg/kg治疗组效果最为显著。结论:SIL对CCl_4所致大鼠肝纤维化及门静脉高压具有抑制作用,其作用机制可能与SIL能够有效保肝降酶,提高NO、cGMP含量有关。

Protective Effects and Mechanisms of Silibinin on the Rats with CCl4-induced Cirrhosis Associated Portal Hypertension

Objective: To study the protective effects and mechanism of silibinin (SIL) on the rats with CCl4-induced cirrhosis and CCl4-induced cirrhosis associated portal hypertension. Methods:All 120 SD rats were randomly divided into normal control group, model control group, SIL (25, 50 and 100 mg/kg) treatment groups and colchicine (0.1 mg/kg) treatment group;cirrhotic portal hypertension rat model was prepared by carbon tetrachloride method. The rats accepted intragastric administration, once a day, for six weeks after the model was prepared. The indexes of liver function were measured:contents of transaminase (ALT, AST) and total bilirubin (TBIL) in serum;Pathological morphological changes of liver tissue were observed by HE staining method;The levels of four hepatic fibrosis (CIV, PCIII, LN, HA) in serum and hydroxyproline (HYP) in liver tissues were measured;The portal venous pressure (PVP), portal venous flow (PVF), mean arterial pressure (MAP), and heart rate (HR) were recorded by physiological recorder;The levels of nitric oxide (NO) and cGMP (cGMP) in liver tissues were measured. Results:Compared with the model control group, the contents of ALT, AST, TBIL, CIV, PCIII, HA and HYP of the rats in SIL (50, 100mg/kg) treatment groups significantly were decreased (P<0.05), PVP and PVF significantly decreased (P<0.05). The contents of NO in liver tissue increased notably (P<0.01);In SIL (100 mg/kg) treatment group, the contents of LN and HR in the serum of the rats decreased significantly while MAP and cGMP in liver tissue increased remarkably, the difference was statistically significant (P<0.05);The pathological morphological changes of liver tissue in SIL treatment group were improved to some extent, especially, SIL 100 mg/kg treatment group the most effective. Conclusion: SIL shows inhibitory action to CCl4-induced liver fibrosis and portal hypertension of rats, and the mechanism may be related to the functions that SIL could protect liver and reduce enzyme, increase the contents of NO and cGMP.