灵芪蠲肝液抗CCl_4诱导的肝损伤机制研究  

Effects of LingQiJuanGan Liquor on CCl_4-induced Chronic Liver Injury in Rats

作　　者：盛云建[1] 吴刚[1] 陈炘[2] 邓存良[1] 

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

出　　处：《天津医药》2012年第3期258-261,I0003,I0004,共6页Tianjin Medical Journal

基　　金：四川省重点学科建设项目(项目编号:SZD0421);泸州医学院青年基金赞助项目(项目编号:06117)

摘　　要：目的:研究灵芪蠲肝液对CCl4实验性肝损伤大鼠Toll样受体4(TLR4)表达的影响。方法:84只Wistar大鼠于0周随机取8只作为正常组,于第1周随机取72只大鼠皮下注射40%的CCl4花生油溶液连续10周造模,第4周随机从造模大鼠中取36只作为治疗组,在造模同时予灵芪蠲肝液治疗,另36只为模型组,2组于4、6、8、10周各随机取8只大鼠同正常组观察以下指标:以逆转录PCR法检测Kupffer细胞(KCs)TLR4mRNA表达,以免疫组织化学法检测肝组织TLR4、核转录因子(NF)-κB蛋白表达;以放免法检测血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β水平,以基质显色终点法检测内毒素水平。结果:与模型组相比,治疗组能明显降低血清TNF-α、IL-1β和内毒素水平,且KCsTLR4mRNA、肝组织TLR4、NF-κB蛋白表达和KnodellHAI炎症积分也明显降低(P<0.05或P<0.01)。血清内毒素水平与KCsTLR4mRNA表达呈正相关(r=0.845,P<0.01)。结论:灵芪蠲肝液可通过降低血清内毒素、KCsTLR4mRNA表达及信号转导,减少炎症因子生成起抗大鼠实验性肝损伤的作用。Objective：To investigate protective effects and mechanism of LingQiJuanGan （LQL） on toll-like receptor 4 （TLR4） in rats with CCl4-induced chronic liver injury. Methods：Eight rats were randomly selected from 84 Wistar rats as normal control group at 0 week. The chronic liver injury was induced by 40% CCl4 injection in rats for 10 weeks. There were 36 rats in model group and 36 rats in therapeutic group. The therapeutic group was given LQL by intragastric administration from the fourth week. The expression of TLR4 mRNA in Kupffer （KCs） was detected by reverse transcriptase polymerase chain reaction （RT-PCR） from 8 rats selected at the end of 4,6,8 and 10-week of the model group and the therapeutic group. The expression levels of TLR4 and nuclear factor kappa B （NF-κB） in hepatic tissue were detected by immunohistochemistry. The serum levels of tumor necrosis factor-α （TNF-α） and interleukin 1β （IL-1β） were detected by radioimmunoassay. The level of serum endotoxin was detected by the end-point chromogenic technique. Results：Compared with the model group,serum levels of TNF-α, IL-1β and endotoxin were significantly decreased in therapeutic group. Expression levels of TLR4 mRNA in KCs, TLR4 and NF-κB in hepatic tissue and Knodell HAI infection scores were also significantly decreased （P 〈 0.05 or P 〈 0.01）. A positive correlation was found between serum endotoxin levels and the expression of TLR4 mRNA in KCs （r = 0.845,P 〈 0.01）. Conclusion： LQL showed the inhibitory effect on the experimental liver injury by anti-inflammation and decreasing serum levels of endotoxin and TLR4 mRNA in KCs.

关 键 词：四氯化碳 创伤和损伤 慢性病 肝脏 肿瘤坏死因子Α TOLL样受体4 大鼠 Wistar 灵芪蠲肝液 

分 类 号：R285.1[医药卫生—中药学]