复方叶下珠汤对四氯化碳致急性肝损伤大鼠的保护作用及机制研究  

Protective Effect and Mechanism of Yexiazhu Decoction on Acute Liver Injury Induced by CCl4 in Rats

作　　者：李梓萌 张可锋[1] 朱依谆 李迎迎[1] 黄书桐 卫文君 高雅[1] Li Zimeng;Zhang Kefeng;Zhu Yizhun;Li Yingying;Huang Shutong;Wei Wenjun;Gao Ya(Guilin Medical University,Guilin 541004)

机构地区：[1]桂林医学院,桂林541004

出　　处：《中药药理与临床》2020年第1期158-163,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：广西壮族自治区教育厅八桂学者专项经费项目(No.桂财教函〔2017〕143号)。

摘　　要：目的:研究复方叶下珠汤对四氯化碳(CCl4)致急性肝损伤大鼠的保护作用,并从Toll样受体4(TLR-4)/核因子κB(NF-κB)炎症信号通路探讨其作用机制。方法:将60只大鼠随机分为正常对照组、模型对照组、水飞蓟素0. 12 g/kg组和复方叶下珠汤12、6、3 g/kg组,每组10只。灌胃等体积相应药物或生理盐水,每天1次,连续给药10 d。末次给药2 h后,正常对照组腹腔注射橄榄油5 m L/kg,其余各组均腹腔注射12%CCl4橄榄油溶液5 m L/kg建立急性肝损伤大鼠模型。禁食不禁水16 h后,摘除眼球取血,采集肝脏。生化法检测血清中ALT、γ-GT和AST活性,肝组织中SOD、GSH-Px及NO和MDA含量;酶联免疫吸附法检测肝组织中TNF-α、IL-6、IL-1β和IFN-γ含量。苏木精-伊红染色(HE染色)观察肝组织病理变化。蛋白质印迹法(Western blot)检测肝组织中TLR-4和NF-κB蛋白的表达情况。结果:与正常对照组比较,模型对照组ALT、AST、γ-GT活力显著升高,SOD、GSH-Px活力、IFN含量明显降低,MDA、NO、TNF-α、IL-1β、IL-6显著增加,TLR-4、NF-κB蛋白表达显著上调(P <0. 05或P <0. 01)。肝组织小叶结构紊乱、肝索排列失序、肝组织水肿。与模型对照组比较,复方叶下珠汤能剂量依赖地降低ALT、AST、γ-GT活性及MDA、NO含量;增强SOD、GSH-Px活性,降低肝组织中TNF-α、IL-1β、IL-6水平,升高IFN-γ含量,抑制TLR-4及NF-κB蛋白表达;病理切片显示复方叶下珠汤对CCl4致急性肝损伤大鼠肝组织的病理变化有改善作用,以6、12 g/kg最为显著(P <0. 05或P <0. 01)。结论:复方叶下珠汤对CCl4致急性肝损伤大鼠有显著的保护作用,其作用机制可能与抑制氧化应激和调控TLR-4/NF-κB信号通路抑制炎症反应有关。Objective: To study the protective effect of Yexiazhu Compound Decoction on rats with acute liver injury induced by CCl4,and to explore its mechanism of TLR-4/NF-κB inflammatory signaling pathway. Methods: 60 rats were randomly divided into the control group,the model group,silybin group( 0. 12 g/kg),and Yexiazhu Compound Decoction groups( 12、6、3 g/kg),10 in each group. Rats were orally administered with corresponding drugs or saline water,daily for 10 consecutive days. 2 hours after the last administration,rats in the control group were intraperitoneally injected with 5 m L/kg olive oil,other rats were intraperitoneally injected with 12% CCl4 dissolved in 5 m L/kg olive oil to establish the acute liver injury model. After fasting for 16 h,the blood was taken from the eyeball,and liver tissues were collected. Biochemical method was used to detect the activities of alanine aminotransferase( ALT),aspartate aminotransferase( AST),Glutamine transferase( γ-GT) in serum,superoxide dismutase( SOD),glutathione peroxidase( GSH-Px),malondialdehyde( MDA) and nitric oxide( NO) in liver tissues. Enzyme-linked immunosorbent assay( ELISA) was used to detect the level of tumor necrosis factor-alpha( TNF-α),interleukin-1β( IL-1β),and interleukin-6( IL-6) and interferon-γ( IFN-γ) in liver tissue. Hematoxylin-eosin staining( HE staining) was used to observe the pathological changes of liver tissues. The protein expressions of TLR-4 and NF-κB in liver tissues of rats were detected by western blot. Results: Compared with the control group,the activities of ALT,AST and γ-GT were increased in the model group,the activities of SOD and GSH-Px were decreased,the content of IFN was decreased,the levels of MDA、NO、TNF-α、IL-1β and IL-6 were significantly increased,the protein expressions of TLR-4 and NF-κB were significantly up regulated. Pathological changes such as lobules disorder,hepatic cords disorder and edema were observed in liver tissues. Compared with the model group,the activities of ALT,AST,γ-GT and the cont

关 键 词：复方叶下珠汤 四氯化碳 急性肝损伤 Toll样受体4/核因子κB信号通路 

分 类 号：R285.5[医药卫生—中药学]