益肝胶囊对刀豆蛋白A所致小鼠肝损伤JAK2/STAT3信号通路的影响

Effects of Yigan Capsule on JAK2/STAT3 signaling pathway in mice with liver injury induced by concanavalin A

目的:研究益肝胶囊对刀豆蛋白A(ConA)所致小鼠肝损伤Janus蛋白酪氨酸蛋白激酶2/信号传导子和转录激活子3(JAK2/STAT3)信号通路的影响及作用机制。方法:50只清洁级雄性小鼠按随机数字表法分为正常组、模型组及益肝胶囊高、中、低剂量组(剂量分别为1.872g/kg、0.936g/kg和0.468g/kg)每组各10只,连续灌胃给药14 d。末次给药后1h,除正常组外其余各组小鼠均一次性尾静脉注射ConA 20mg/kg诱导小鼠肝损伤,禁食不禁水8 h后处死。检测血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、白介素6(IL-6)、肿瘤坏死因子а(TNF-а)和γ干扰素水平,Western blot法检测肝组织中细胞因子信号传导抑制因子3(SOCS-3)、p-JAK2和p-STAT3蛋白表达,HE染色观察肝组织的病理变化。结果:与模型组比较,益肝胶囊各剂量组小鼠血清中ALT、AST、IL-6、TNF-α和IFN-γ水平显著降低;肝组织中p-JAK2、p-STAT3蛋白表达显著降低,SOCS-3蛋白表达显著升高,益肝胶囊各剂量组小鼠肝组织的病理损伤程度均有明显减轻。结论:益肝胶囊可能通过SOCS-3调控JAK2/STAT3信号通路以抑制炎症反应,从而起到肝保护作用。

Objective:To study the liver-protecting function and mechanism of Yigan-capsule on JAK2/STAT3 signal pathway of Liver Injury by Concanavalin A in Mice.Methods:SPF mice were randomly divided into normal group,model group,Yigan-capsule high dose,Yigan-capsule medium dose and Yigan-capsule low dose groups,with ten rats in each groups.The Yigan-capsule groups were given corresponding drugs with intragastric administration once a day for 14d.1h after last administration,All the mice except those in normal group received Con A(20mg·kg-1)by injection via tail vein to induce mice liver injury model.Lasting for 8 h,the content of ALT,AST,IL-6,TNF-α,IFN-γin serum were measured,and the protein expression of SOCS3,p-JAK2 and p-STAT3 in liver tissue were detected by Western blot;the liver tissue pathological change was deteced by HE staining method by using microscope observation.Results:Compared with model group,the content of ALT,AST,IL-6,TNF-α,IFN-γin serum of Yigan-capsule groups were decreased significantly;the protein expression of p-JAK2 and p-STAT3 in liver tissue were decreased,the expression of SOCS3 in liver tissue was increased significantly;and the pathological sections showed that the hepatic injury were relieved clearly.Conclusion:Yigan-capsule has a significant hepatoprotective effect,of which mechanism may be related to the inhibition of inflammatory response,and regulate the JAK2/STAT3 signaling pathway by mediating SOCS-3.