清热化瘀中药对急性肝衰竭模型大鼠肝功能及生存期的影响

目的:探讨清热化瘀中药对急性肝衰竭(acuteliver failure,ALF)模型大鼠肝功能及生存期的影响.方法:采用D-氨基半乳糖(D-GalN)单次腹腔注射构建ALF大鼠模型,125只SD大鼠以是否接受造模和药物干预随机分为空白组、模型组、复方甘草酸苷组和清热化瘀中药组;每组再以36、96h两个时间点继续随机分为1、2两个亚组,共8组,其中亚组1用于造模后36h取血及肝组织标本,亚组2用于观察96h内大鼠的生存率.以全自动生化分析法检测血清丙氨酸氨基转移酶(alanineaminotransferase,ALT)、门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、总胆红素(total bilirubin,TBIL)、白蛋白(albumin,ALB)和胆碱酯酶(cholinesterase,CHE),全自动血凝分析法检测血浆凝血酶原时间(prothrombintime,PT),常规HE染色作肝组织病理学观察.结果:模型组、复方甘草酸苷组及清热化瘀中药组估计平均生存时间分别为64.6、71.9、83.3h;log-rank检验提示清热化瘀中药组累积生存率高于模型组(2=4.428,P<0.05).与模型组相比,空白组、清热化瘀中药组和复方甘草酸苷组血清ALT、AST、TBIL及血浆PT水平均显著下降(P<0.01),清热化瘀中药组低于复方甘草酸苷组(P<0.01).与模型组相比,空白组、清热化瘀中药组和复方甘草酸苷组在血清ALB和CHE水平均明显升高(P<0.01),清热化瘀中药组高于复方甘草酸苷组(P<0.01).与模型组相比,清热化瘀中药组和复方甘草酸苷组肝组织损伤程度积分明显下降(1.84±0.13,2.85±0.20vs3.56±0.24,均P<0.01),清热化瘀中药组低于复方甘草酸苷组(P<0.01).结论:清热化瘀中药可显著减轻D-GalN诱导急性肝衰竭大鼠肝细胞的损伤,改善肝功能及肝脏病理并降低ALF模型大鼠的病死率、延长生存期,对ALF患者有潜在的临床应用价值.

Effect of herbs for clearing heat and resolving stasis on liver function and survival in rats with acute liver failure

AIM:To investigate the effect of herbs for clearing heat and resolving stasis on liver function and survival in rats with acute liver failure(ALF).METHODS:Rats were intraperitoneally injected with D-GalN(1.4 g/kg) to induce ALF.One hundred and twenty-five SD rats were randomly divided into four group:normal group,model group,Stronger Neo-Minophagen C(SNMC) group,and Qingre Huayu herbs group according to whether or not to undergo ALF induction and interventional drugs.Each group was further randomly divided into two subgroups for testing at different time points.One subgroup was used to collect blood and liver tissue samples,while the other was applied to observe the survival of rats 96 h after ALF induction.Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),albumin(ALB),cholinesterase(CHE) and plasma prothrombin time(PT) were measured,and hepatic histopathological changes were observed by microscopy after HE staining.RESULTS:After 96-hour treatment,mean survival time of rats in the three groups were 64.6,71.9,and 83.3 h,respectively.The cumulative survival rate of rats in the Qingre Huayu herbs group was higher than that of rats in the model group(2 = 4.428,P < 0.05).Compared to the model group,the levels of serum ALT,AST,TBIL and plasma PT were remarkably reduced in the normal group,Qingre Huayu herbs group,and SNMC group(all P < 0.01).The levels of serum ALT,AST,TBIL and plasma PT were significantly lower in the Qingre Huayu herbs group than in the SNMC group(all P < 0.01).Compared to the model group,liver pathological score was significantly lower in the Qingre Huayu herbs group and SNMC group(1.84 ± 0.13,2.85 ± 0.20 vs 3.56 ± 0.24,both P < 0.01),and in the Qingre Huayu herbs group than in the SNMC group(P < 0.01).In contrast,the levels of serum ALB and CHE were significantly higher in the normal group,Qingre Huayu herbs group,and SNMC group(all P < 0.01) than in the model group,and in the Qingre Huayu herbs group than in the SNMC group(P < 0.01).CONCLUSION:Qingre Huayu herbs can significantly relieve liver cell’s damage,improve liver function and liver pathology,reduce mortality,extend survival time in D-GalN-induced acute liver failure rats,which indicated its potential use in patients with ALF.