齐墩果酸对四氯化碳诱导大鼠肝硬化门静脉高压的影响

目的:研究齐墩果酸(Oleanolic acid,OA)对四氯化碳(CCl4)诱导的大鼠肝硬化门静脉高压的影响及其可能的作用机制。方法:大鼠采用CCl4灌胃给药诱发肝硬化门静脉高压,给予OA低(30 mg/kg)、高(60 mg/kg)剂量治疗,正常对照组与模型组给予等容积溶剂。1个月后分别测定血清中丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)等血清生化指标及肝组织中丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、NOx、内皮型一氧化氮合酶(eNOS)、环磷酸鸟苷(cGMP)、I型胶原蛋白的含量;采用血液动力学的方法测定大鼠主动脉的血压(MAP)、门静脉压(PP)、心率(HR)等指标;采用Western blotting技术测定肝硬化大鼠eNOS的表达;采用Masson染色对大鼠肝纤维化的进展进行研究。结果:与模型组比较,给予OA治疗1个月后显著降低血清ALT、AST、ALP、γ-GT、MDA的水平和提高肝组织中GSH-Px的含量(P0.05);显著降低模型大鼠肝脏的胶原沉积及肝纤维化的进展,进而降低了门静脉压(P0.05),而主动脉压(MAP)和心率(HR)无显著变化;并能显著提高肝内eNOS蛋白表达水平,进而提高了肝硬化大鼠肝内的cGMP和NOx的含量(P0.05)。结论:OA对四氯化碳诱导大鼠肝硬化门静脉高压具有良好的治疗作用,其作用机理可能是通过促进肝内的eNOS蛋白表达从而提高肝内NOx的含量。

The Anti-portal Hypertension Effect of Oleanolic Acid in CCl4-induced Cirrhosis Rats

Objective:To study the anti-portal hypertension effect of oleanolic acid(OA)in CCl4-induced cirrhosis rats and its mechanism.Methods:Rats were induced to portal hypertension by CCl4.After treatment with low dose of OA(30 mg/kg)and high dose of OA(60 mg/kg)by intragastrically for a month,the parameters in serum or liver tissue including ALT,AST,MDA,GSH-Px,NOx,eNOS,cGMP and type I collagen were measured.The MAP,PP and HR were determined by hameodynamic method and the eNOS expression in liver was measured by western blot.The pathological changes of liver tissue were also tested by Masson dye.The normal group and model group were given 0.25% of CMC-Na solution.Results:Compared with the model group,treatment with 30 mg/kg and 60 mg/kg OA significantly decreased the levels of ALT,AST,ALP,γ-GT and MDA and enhanced the level of GSH-Px in liver(P<0.05).Moreover,the collagen content also notably lowered in CCl4-induced cirrhosis rats,thus decreasing the portal pressure(PP).However,the MAP and HR were not affected by OA treatment.In addition,the expression of eNOS in liver markedly increased after one mouth treatment of OA,hereof enhancing the level of cGMP and NOx in the CCl4-induced portal hypertensive rats(P<0.05).Conclusion:OA could inhibit the progress of fibrosis and lower the PP in CCl4-induced portal hypertensive rats and the anti-portal hypertension effect might be related to increasing the expression of eNOS and enhance the NOx level in liver.