扶正化瘀方对DMN肝硬化模型大鼠门静脉压力的影响

Effects of Fuzheng Huayu Decoction on elevated portal pressure in rat model of dimethylnitrosamine-induced liver cirrhosis

目的:研究扶正化瘀方对肝硬化门静脉高压的影响.方法:以5g/L的二甲基亚硝胺(DMN)ip4wk建立大鼠肝硬化的动物模型,中药治疗3wk后,肠系膜上静脉插管测定门静脉压力,测定肝组织中羟脯氨酸(Hyp)和内皮素(ET-1)的含量,测定血清丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)活性和白蛋白(ALB)和总胆红素(TBIL)含量,观察肝组织病理形态的变化.结果:模型组大鼠门静脉压力显著升高,升高幅度为正常组的2.4倍;肝组织ET-1含量较正常大鼠增加明显(344.48±71.42pg/mgvs247.00±49.51pg/mg,P<0.01);肝硬化大鼠此2项指标呈显著正相关(r=0.675,P<0.01).而经扶正化瘀方治疗的大鼠,门静脉压力较模型组下降约67%(P<0.01),ET-1含量为292.13±52.07pg/mg(P<0.05).治疗组大鼠血清ALT、AST、TBIL水平及肝组织Hyp和ET-1含量与模型组比较也都有显著下降,病理观察显示治疗组大鼠肝脏结构基本恢复正常.结论:肝硬化时大鼠门静脉压力升高与肝组织ET-1含量的增高呈正相关,扶正化瘀方通过抗肝纤维化显著降低肝硬化模型大鼠升高的肝组织ET-1含量和门静脉压力.

AIM： To investigate the effect of Fuzheng Huayu Decoction （FHD） on portal hypertension due to liver cirrhosis induced by dimethylnitrosamine （DMN）. METHODS： After the rat model of hepatic cirrhosis was successfully established via intraperitoneal injection of 5 g/L DMN, traditional Chinese medicine formula FHD was administrated intragastrically. Three weeks later, serum levels of alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, albumin （ALB） and total bilirubin （TBIL）, as well as hepatic levels of hydroxyproline （Hyp） and endothelin-1 （ET-1） were measured. For portal pressure measurement, a catheter was inserted into the superior mesenteric vein and gently advanced up to the portal vein. The pathological alterations of liver tissues were observed and compared between control group and treatment group. RESULTS： Portal pressure of the model group was 2.4 times higher than those in normal group; the ET-1 contents in liver tissue significantly increased in comparison with that of normal group （344.48 ± 71.42 pg/mg vs 247.00 ± 49.51 pg/mg, P 〈 0.01）. The above two markers in model group were positively correlated （r = 0.675, P 〈 0.01）. Portal pressure of the treatment group remarkably declined by 67% （P 〈 0.01） and ET-1 contents remarkably dropped to 292.13 ± 52.07 pg/mg （P 〈 0.05）. There were signifi- cant differences between the treatment group and model group in the serum levels of ALT, AST, and TBIL and Kssue contents of Hyp and ET-1. Pathological findings showed restoration of normal liver structure in the treatment group. CONCLUSION： The elevation of portal pressure is positively correlated with the increase of ET-1 content during the process of liver cirrhosis; FHD can significantly decrease the cirrhosis- induced elevation of portal pressure and ET-1 content in liver tissues through its anti-hepatic fibrosis effect in rats.