摘要
目的:观察黄芪建中汤对四氯化碳诱导的肝纤维化大鼠JAK/STAT信号通路的调节作用。方法:60只大鼠随机分为对照组、模型组、黄芪建中汤组及阳性对照组,15只/组,除对照组外,其余大鼠采用腹腔注射四氯化碳的方法建立肝纤维化大鼠模型,黄芪建中汤组根据大鼠体重按照10 ml/kg的的剂量灌胃给予大鼠黄芪建中汤,阳性对照组灌胃给于大鼠秋水仙碱(0.2 mg/kg),1次/d,连续给药60 d,检测大鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、γ-谷氨酰转肽酶(GGT)、透明质酸酶(HA)、层黏连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(ColⅣ)水平、大鼠肝组织超氧化物歧化酶(SOD)活性及丙二醛(MDA)、肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)、白介素-6(IL-6)水平、肝组织JAK2、STAT3 mRNA及各组大鼠肝组织JAK2、STAT3、p-JAK2、p-STAT3蛋白表达,采用苏木精-伊红染色法(HE)及Masson染色对大鼠肝组织病理学进行检查。结果:给予肝纤维化模型大鼠黄芪建中汤后,黄芪建中汤组大鼠血清ALT、AST、ALP、GGT[(43.49±0.56)、(47.36±1.05)、(78.46±1.46)、(3.33±0.17)]U/L,HA、LN、PCⅢ、ColⅣ[(146.44±2.63)、(91.60±1.86)、(102.41±1.71)、(41.60±1.38)]ng/ml水平,大鼠肝组织MDA(4.36±0.13)nmol/mg prot、TNF-α(113.44±1.40)ng/mg、IL-1β及IL-6[(156.90±1.64)、(125.07±1.41)]pg/mg水平、肝组织中JAK2(1.24±0.17)及STAT3(1.31±0.26)m RNA水平及JAK2(0.59±0.08)、STAT3(0.70±0.06)、p-JAK2/JAK2(0.51±0.04)及p-STAT3/STAT3(0.47±0.09)水平较模型组肝纤维化大鼠显著降低(P<0.05),SOD(100.94±1.26)U/mg prot活性升高(P<0.05),肝组织病理学改善。结论:黄芪建中汤组能够明显改善大鼠肝功能,降低肝纤维化大鼠肝纤维化水平及肝脏氧化应激损伤,其机制可能与调节JAK/STAT信号通路有关。
Objective:To study the regulatory effect of Huangqi Jianzhong decoction on the JAK/STAT signal pathway in rats with hepatic fibrosis induced by carbon tetrachloride.Methods:A total of 60 rats were randomly divided into the control and model group,the Huangqi Jianzhong decoction group,and the positive control group.Except for the control group,the rat model of hepatic fibrosis was established by intraperitoneal injection of carbon tetrachloride.The Huangqi Jianzhong decoction group was given Huangqi Jianzhong decoction according to the body weight of rats.The positive control group was given intragastric administration of 0.2 mg/kg based on colchicine,and the control group and model group were given the same amount of normal saline once a day for 60 days.The levels of serum glutamic pyruvic transaminase(ALT),glutamic oxaloacetic transaminase(AST),alkaline phosphatase(ALP),γglutamyl transpeptidase(GGT),hyaluronidase(HA),laminin(LN),typeⅢprocollagen(PCⅢ),typeⅣcollagen(ColⅣ),superoxide dismutase(SOD)activity and malondialdehyde(MDA)level,levels of tumor necrosis factorα(TNF-α),interleukin 1β(IL-1β)and interleukin 6(IL-6)in rat liver were measured.The pathological changes in rat liver tissue were detected by hematoxylin-eosin staining and Masson staining,and the levels of JAK2 and STAT3mRNA in rat liver tissue were detected by real-time quantitative PCR.The protein levels of JAK2、STAT3、p-JAK2、p-STAT3 in rat liver tissue were detected by Western blot.Results:Compared with the model group,the levels of serum ALT、AST、ALP、GGT[(43.49±0.56),(47.36±1.05),(78.46±1.46),(3.33±0.17)]U/L,HA,LN,PCⅢ,ColⅣ[(146.44±2.63),(91.60±1.86),(102.41±1.71),(41.60±1.38)]ng/ml in Huangqi Jianzhong decoction group,the level of MDA(4.36±0.13)nmol/mg prot,TNF-α(113.44±1.40)ng/mg、IL-1βand IL-6[(156.90±1.64),(125.07±1.41)]pg/mg in liver tissue,the level of JAK2 and STAT3 mRNA in liver tissue and the level of JAK2(0.59±0.08),STAT3(0.70±0.06),p-JAK2/JAK2(0.51±0.04)and p-STAT3/STAT3(0.47±0.09)protein in liver tissue were significantly decreased(P<0.05),while the activity of SOD(100.94±1.26)U/mg prot in liver tissue was significantly increased(P<0.05).Conclusion:Huangqi Jianzhong decoction group can significantly improve the liver function and the level of hepatic fibrosis factors,reduce the oxidative stress injury of liver tissue,and improve the pathological changes of liver tissue,and its mechanism may be related to the regulation of JAK/STAT signal pathway.
作者
张学政
吴冬冰
张学娟
吴冬寒
ZHANG Xue-zheng;WU Dong-bing;ZHANG Xue-juan;WU Dong-han(Second Ward of Digestive Internal Medicine,Sanya People′s Hospital(Hainan Sanya,572100),China.)
出处
《中西医结合肝病杂志》
CAS
2023年第9期800-804,809,共6页
Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases
基金
海南省卫生健康行业科研项目(No.20A200524)。
作者简介
通讯作者:吴冬寒,E-mail:wdh6002@sohu.com。
