基于JAK2/STAT3信号通路探究鬼箭羽醇提物抗CCl_(4)诱导C57BL/6J小鼠肝纤维化作用机制  

Effects of ethanolic extracts of Euonymus alatus on CCl 4-induced hepatic fibrosis in mice based on JAK2/STAT3 signaling pathway and its mechanism

作　　者：王咏兰 陶柏楠 陈明环 曾华华 马敏 黄德斌 WANG Yong-lan;TAO Bo-nan;CHEN Ming-huan;ZENG Hua-hua;MA Min;HUANG De-bin(Hubei Minzu University,Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases,Enshi,Hubei 445000,China)

机构地区：[1]湖北民族大学风湿性疾病发生与干预湖北省重点实验室,湖北恩施445000

出　　处：《中国药理学通报》2023年第5期875-881,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82060745);风湿性疾病发生与干预湖北省重点实验室(湖北民族大学)开放基金项目(No PT022213)。

摘　　要：目的基于JAK2/STAT3信号通路探究鬼箭羽醇提物抗CCl_(4)诱导C57BL/6J小鼠肝纤维化(hepatic fibrosis,HF)作用机制。方法将60只C57BL/6J小鼠随机分为空白组、模型组、鬼箭羽低剂量组(EAL)、鬼箭羽中剂量组(EAM)、鬼箭羽高剂量组(EAH)、水飞蓟宾(Silybin)阳性治疗组,每组10只。除正常组外,其余小鼠腹腔注射25%CCl_(4)花生油液1.6 mL·kg^(-1)诱导HF模型。同时,阳性治疗组给予12.6 mg·kg^(-1)的水飞蓟宾,EAL、EAM、EAH分别给予鬼箭羽醇提物72、140、280 mg·kg^(-1),每日1次,连续6周。当第6周治疗结束,空腹称质量,采血取肝,观察肝脏外形,计算肝脏指数,检测小鼠血清中ALT、AST、TNF-α、IL-6、IL-1β。检测肝组织α-SMA、Collagen-Ⅰ和JAK2/STAT3信号通路相关蛋白(JAK2、STAT3、p-JAK2、p-STAT3)表达。结果与模型组相比,EAM和EAH明显降低CCl_(4)导致的肝脏指数增加,抑制血清ALT、AST、α-SMA、collagen I升高;鬼箭羽干预组的肝形态结构、细胞炎性浸润、纤维变化及胶原沉积呈剂量依赖性优于模型组;EAM、EAH血清中TNF-α、IL-6和IL-1β表达明显低于模型组(P<0.05),肝组织中与JAK2/STAT3信号通路有关的JAK2、STAT3、p-JAK2、p-STAT3蛋白表达也明显低于模型组(P<0.05)。结论鬼箭羽醇提物具有抗CCl_(4)诱导小鼠HF作用,其机制可能与JAK2/STAT3信号通路的调控有关。Aim To explore the mechanism of ethanolic extracts of euonymus alatus on CCl_(4)-induced hepatic fibrosis in mice by regulating JAK2/STAT3 signaling pathway.Methods Sixty C57BL/6J mice were randomly divided into control group,model group,EAL,EAM,EAH,and Silybin(n=10).Except for the control group,mice in other groups were injected with 25%CCl_(4)of 1.6 mL·kg^(-1)to induce HF model.Moreover,the positive group was administered 12.6 mg·kg^(-1)Silybin by gavage once a day,and EAL,EAM,and EAH were administered 72,140 and 280 mg·kg^(-1)ethanolic extracts of euonymus alatus once by gavage once a day,and the intervention lasted for six weeks.After 6th week,mouse blood was collected,the body weight and liver weight were measured and liver mass index calculated,the liver appearance was observed,and ALT,AST,TNF-α,IL-6,IL-1β were detected in serum.The protein expression levels of collagenⅠ,α-SMA,and JAK2/STAT3 signaling pathway-related protein(JAK2,STAT3,p-JAK2,p-STAT3)in mouse liver tissues were detected.Results Compared with the model group,EAM and EAH significantly decreased liver mass index,and the ALT,AST,α-SMA,collagen I levels of serum.After treatment,the liver morphology and structure,cellular inflammatory infiltration,fiber changes and collagen deposition in euonymus alatus intervention group were dose-dependently better than those of the model group.Compared with the model group,the expression of TNF-α,IL-6 and IL-1βin EAM and EAH serum decreased significantly(P<0.05).Compared with the model group,the protein expression levels of JAK2,STAT3,p-JAK2,p-STAT3 in EAM and EAH mouse liver tissues decreased significantly(P<0.05).Conclusion Ethanolic extracts of euonymus alatus have an anti-CCl_(4)-induced HF effect in mice,and its mechanism may be related to the regulation of the JAK2/STAT3 signaling pathway.

关 键 词：鬼箭羽醇提物 肝纤维化 TNF-α JAK2 STAT3 IL-6 

分 类 号：R-332[医药卫生] R284.1R322.47R345.57R392.12R575.2