大黄对急性肝衰竭大鼠肝脏过氧化损伤及HIF-1α表达的影响

Effects of Rhubarb on the Damage of Peroxidation and the Expression of HIF-1α in Livers of Acute Liver Failure Rats

目的:观察大黄对急性肝衰竭模型大鼠肝脏过氧化损伤及HIF-1α表达影响。方法:雄性SD大鼠55只,随机分为健康对照组(15只)、肝衰竭组(20只)、大黄干预组(20只)。采用腹腔注射硫代乙酰胺(TAA)法复制急性肝衰竭模型,造模前一天,大黄干预组予大黄煎剂2mL/只灌胃,健康对照组和肝衰竭组予生理盐水2mL/只灌胃,均1天3次,连续3天。造模48h后对各组存活大鼠行门静脉采血,测定各组血清ALT、AST、TBiL、内毒素水平、肝脏组织MDA含量、SOD活性;免疫组化检测肝组织HIF-1α表达,常规HE染色观察肝脏病理学改变。结果:与健康对照组比较,肝衰竭组大鼠ALT、AST、TBiL升高(P<0.01),血清内毒素含量增高(P<0.01),肝脏内SOD活力降低(P<0.01),MDA含量升高(P<0.01),肝组织HIF-1α表达增加(χ2=11.49,P<0.01);与肝衰竭组比较,大黄干预组大鼠ALT、AST、TBiL下降(P<0.01,P<0.05);血清内毒素含量降低(P<0.05);肝脏内SOD活力升高(P<0.01),MDA含量降低(P<0.01)。肝衰竭组大鼠肝脏内HIF-1α表达增强(P<0.01),但与大黄干预组比较,两组差异无统计学意义(χ2=0.316,P>0.05)。结论:肝衰竭大鼠肝脏存在过氧化损伤,HIF-1α表达增加。大黄能改善急性肝衰竭模型大鼠肝功能,减轻内毒素血症及过氧化损伤。

Objective：To investigate the effects of Rhubarb on the damage of oxygen free radical and the expression of HIF-1αin livers of acute liver failure rats.Methods： The rats were intraperitoneally injected with thioacetamide to induce the model of acute liver failure.A total of fifty-five male Sprague-Dawley rats were randomly divided into 3 groups： normal control group（n=15）,liver failure group（n=20）,and rheum-administrated group（n=20）.The rheum-administrated group received rheum solution by gavage initiated 24 h prior to the first TAA injection.The control groups were all treated with saline as a control.Forty-eight hours later,rats alive were killed and the portal vein blood was collected.The indexes of serum ALT,AST,TB,endotoxin were assayed;the concentration of SOD/MDA was detected;the expression of HIF-1α was evaluated;and the histopathological changes of livers was observed.Results： Compared with the normal control group,serum levels of ALT,AST,TB,and endotoxin in the liver failure group were markedly higher（P0.01,P0.05）;the level of SOD in livers was significantly lower（P0.01） and MDA was higher;and the expression of HIF-1αwas significantly higher（χ2=11.49,P0.01）.After the treatment of rheum,compared with the liver failure group,the levels of ALT,AST,and TB were significantly reduced（P0.01）,the level of endotoxin was downregulated（P0.05）,and SOD was higher（P0.01）,MDA was lower（P0.01）;while the expression of HIF-1α did not differ in the 2 groups（χ2=0.316,P0.05）.Conclusions： Rhubarb can improve the liver function of acute liver failure in rats by resistant to the damage of oxygen free radical and attenuating endotoxemia.