八宝丹对急性肝衰竭大鼠肝性脑病的防治作用  

Preventive and therapeutic effects of Babaodan on hepatic encephalopathy in rats with acute liver failure

作　　者：陆璐 武超[1,2] 谢咚 安泳潼[3] 赵亚红[3] 叶冠[3] 孙明瑜[1,2] LU Lu;WU Chao;XIE Dong(Key Laboratory of Liver and Kidney Diseases(Ministry of Education),Institute of Liver Diseases,Shuguang Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院,上海中医药大学肝病研究所,肝肾疾病病证教育部重点实验室,上海201203 [2]上海中医药大学,上海201203 [3]上海医药集团股份有限公司中央研究院,上海201203

出　　处：《临床肝胆病杂志》2018年第12期2635-2641,共7页Journal of Clinical Hepatology

基　　金：上海市科委专项(15DZ1900104);国家自然科学基金项目(81273729);国家中医药管理局第四批全国中医优秀人才研修项目(2017)

摘　　要：目的探讨八宝丹对急性肝衰竭大鼠肝性脑病的防治作用及机理。方法将50只Wistar大鼠随机分为5组,即正常组、模型组、八宝丹低剂量组、八宝丹高剂量组和乳果糖组。各治疗组每天予以相应药物灌胃1次,正常组和模型组予以同体积0. 3%的羧甲基纤维素钠;灌胃第4天,以硫代乙酰胺(350 mg/kg)腹腔注射诱导肝性脑病,正常组注射等体积生理盐水,每24 h注射1次,共注射3次进行造模,造模后12 h,处死大鼠。HE染色观察肝和脑组织的病理变化,试剂盒检测血氨和肝功能指标,RT-PCR法检测肝组织和脑组织的基因变化。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果与模型组比较,八宝丹低剂量组和高剂量组的血氨、TBil、TBA、ALT和AST水平均明显降低(P值均<0. 05),TP水平明显升高(P值均<0. 05),八宝丹高剂量组的Alb水平明显升高(P <0. 05)。八宝丹低剂量组和高剂量组肝组织的坏死、炎症均显著改善,脑组织的坏死、核固缩减轻。与模型组相比,八宝丹低剂量组和高剂量组肝组织的TNFα、IL-1、IL-6、NF-κB、Bax、Caspase-3和Caspase-8 mRNA均显著下调(P值均<0. 05),八宝丹高剂量组的Bcl-2 mRNA则显著上调(P <0. 05);八宝丹低剂量组和高剂量组脑组织的IL-1、TNFα、iNOS和GS mRNA均显著下调(P值均<0. 05)。结论八宝丹可以有效调节炎症因子表达,抑制肝细胞凋亡坏死,减少血氨生成及炎性浸润,从而缓解脑损伤,治疗急性肝衰竭大鼠的肝性脑病。Objective To investigate the preventive and therapeutic effects of Babaodan on hepatic encephalopathy in rats with acute liver failure and possible mechanisms.Methods A total of 50 Wistar rats were randomly divided into normal group,model group,low-dose Babaodan group,high-dose Babaodan group,and lactulose group.The rats in the low-dose Babaodan group,the high-dose Babaodan group,and the lactulose group were given the corresponding drugs by gavage once a day,and those in the normal group and the model group were given an equal volume of 0.3%sodium carboxymethyl cellulose.On day 4 of gavage,intraperitoneal injection of thioacetamide(350 mg/kg)was performed to induce hepatic encephalopathy,and the rats in the normal group were injected with an equal volume of normal saline,once every 24 hours for 3 times.The rats were sacrificed at 12 hours after the last injection.HE staining was used to observe pathological changes of the liver and the brain;related kits were used to measure blood ammonia and liver function parameters;RT-PCR was used to measure the changes in related genes in liver and brain tissues.The one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the model group,the low-and high-dose Babaodan groups had significant reductions in the levels of blood ammonia,total bilirubin,total bile acid,alanine aminotransferase,and aspartate aminotransferase(all P<0.05)and a significant increase in total protein level(P<0.05),and the high-dose Babaodan group had a significant increase in albumin(P<0.05).Both the low-and high-dose Babaodan groups had significant improvements in liver necrosis and inflammation and brain necrosis and karyopyknosis.Compared with the model group,the low-and high-dose Babaodan groups had significant reductions in the mRNA expression of tumor necrosis factor-α(TNF-α),interleukin-1(IL-1),interleukin-6,nuclear factor-kappa B,Bax,caspase-3,and caspase-8 in

关 键 词：肝性脑病 肝功能衰竭 急性 八宝丹 大鼠 Wistar 

分 类 号：R575.3[医药卫生—消化系统]