灵芪蠲肝液对大鼠TLR4信号途径的影响  

THE EFFECT OF LINGQIJUANGAN LIQUOR ON TOLLLIKE RECEPTOR 4 SIGNALING IN RATS WITH CHRONIC LIVER INJURY

作　　者：邓存良[1] 陈炘[2] 盛云建[1] 陈文[1] 

机构地区：[1]泸州医学院附属医院感染科,四川泸州646000 [2]内江市第一人民医院感染科

出　　处：《泸州医学院学报》2011年第5期495-500,共6页Journal of Luzhou Medical College

基　　金：中国肝炎防治基金会王宝恩肝纤维化防治基金研究课题(2010-jxs003);四川省科技厅项目(2006Z08-087)

摘　　要：目的:探讨四氯化碳(CCl4)诱导大鼠肝损伤的作用机制,并观察灵芪蠲肝液对Toll样受体4(TLR4)信号传导途径的影响。方法:雄性健康Wistar大鼠,设置模型组、灵芪蠲肝组(治疗组)和空白组。用40%CCl4花生油溶液皮下注射建立慢性肝损伤模型,以灵芪蠲肝液灌胃作治疗性研究,于第8周收集血液和肝脏组织。检测肝功能ALT、AST、白蛋白(ALB)水平;检测血清内毒素、白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)水平;分离枯否细胞(KCs),采用逆转录-聚合酶链式反应(RT-PCR)检测KCs TLR4 mRNA表达;肝组织HE染色,按Knodell HAI评分标准对肝脏炎症评分,免疫组化SP法检测肝组织TLR4和核因子κB(NF-κB)蛋白表达。结果:空白组除ALB高于模型组和治疗组外,其余指标均最低。模型组血清ALT、AST、内毒素、IL-1β、TNF-α水平明显高于治疗组(P<0.001),ALB水平明显低于治疗组(P<0.05),KCs TLR4 mRNA表达明显高于治疗组(P<0.001),肝组织炎症Knodell HAI评分、TLR4和NF-κB蛋白均高于治疗组(P<0.001)。结论:①通过TLR4信号传导途径释放炎症介质致肝组织损伤可能为CCl4诱导慢性肝损伤的机制之一。②灵芪蠲肝液治疗慢性肝损伤的机制可能与抑制TLR4信号途径有关。Objective： To investigate the mechanism of chronic liver injury induced by CCl4,and to observe the role of TLR4 signaling in mechanism of chronic liver injury.Methods：Male wistar rats were randomly divided into normal control group,model group and Lingqijuangan group（therapeutic group）.The chronic liver injury was induced by hypodermic injection of 40% CCl4,and the therapeutic group was given Lingqijuangan Liquor by intragastric administration.Blood and liver were collected at the same time at the end of the 8th week.The plasma IL-1β,TNF-α and endotoxin levels were detected.Rat Kupffer cells（KCs） were separated,and the expressions of TLR4 mRNA in Kupffer cells were measured by reverse transcriptase polymerase chain reaction（RT-PCR）.Liver tissues were stainned by HE,and liver inflammation was measured with histological activity index（Knodell HAI）.The expression of TLR4 and nuclear factor-κB（NF-κB） protein in hepatic tissue was assayed by immunohistochemistry.Results： Serum ALT,AST,endotoxin,IL-1β and TNF-α were higher in model group than in therapeutic group,and they were the lowest in normal control group（P〈0.001）.Serum ALB was the highest in normal control group,and it was higher in therapeutic group than in model group（P〈0.001）.The expression of TLR4 mRNA in KCs,Knodell HAI of inflammation,TLR4 and NF-κB protein in hepatic tissue was higher in model group than in therapeutic group（P〈0.001）.Conclusion： Releasing of inflammation mediators through signaling pathway of TLR4 is one of the mechanisms of chronic liver injury induced by CCl4.The therapeutical effect of Lingqijuangan Liquor is probably involved with the inhibition of the signaling pathway of TLR4,which may play a singnificant role in the mechanism of chronic liver injury.

关 键 词：灵芪蠲肝液 慢性肝损伤 炎症介质 TLR4 信号传导 

分 类 号：R575.1[医药卫生—消化系统]