JNK抑制剂XG-102对非酒精性脂肪性肝炎大鼠的保护作用及其机制  

Impact of JNK inhibitor XG-102 in a diet-induced rat model of non-alcoholic steatohepatitis

作　　者：胡迎宾[1] 彭娜[1] 雷德利[1] 程方雄[1] 陈以莲[1] 

机构地区：[1]华中科技大学同济医学院附属普爱医院消化内科,武汉430033

出　　处：《中华肝脏病杂志》2014年第12期948-952,共5页Chinese Journal of Hepatology

基　　金：武汉市卫生局临床科研项目（WX12C33）

摘　　要：目的 观察JNK抑制剂XG-102对高脂饮食诱导大鼠非酒精性脂肪性肝炎的治疗作用,并探讨其机制. 方法 通过手术对48只雄性SD大鼠建立经皮肠系膜上静脉给药通路,10d后将SD大鼠随机均分为对照组,模型组和治疗组.通过高脂饮食建立大鼠非酒精性脂肪性肝炎模型,其中治疗组在高脂饮食喂养12周后,同时给予JNK抑制剂XG-102（1 mg/kg）经皮肠系膜上静脉注射治疗4周.16周末观察肝脏病理组织学变化,检测血清ALT、AST、总胆固醇（TC）、甘油三脂（TG）、空腹胰岛素、空腹血糖、游离脂肪酸（FFAs）和肿瘤坏死因子α（TNF α）水平,计算稳态模型的胰岛素抵抗指数（HOMA-IR）,用Westem blot方法检测肝组织phospho-c-Jun和cleavedcaspase-3蛋白的表达水平.两组间比较用t检验,多组间比较采用方差分析,均数间的两两比较采用Student-Newman-Keuls检验,并进行方差齐性检验.计数资料组间比较采用x2检验.结果 对照组ALT、AST、TC、TG、FFAs、HOMA-IR和TNF-α分别为（41.3±4.8） U/L、（96.9±9.8）U/L、（1.11±0.19） mmol/L、（0.74±0.11） mmol/L、（353.1±36.4） μmol/L、3.20±0.39、（6.74±1.21） pg/ml,模型组分别为（118.3±11.6） U/L、（163.9±16.2）U/L、（3.45±0.49）mmol/L、（1.89±0.25） mmol/L、（613.2±64.1）μmol/L、6.97±0.72、（25.01±5.37） pg/ml,治疗组分别为（86.5±8.3） U/L、（130.6±13.4） U/L、（2.62±0.32） mmol/L、（1.14±0.19）mmol/L、（512.1±51.9）μmol/L、4.34±0.48、（19.96±4.19） pg/ml.与对照组比较,模型组血清ALT、AST、TC、TG、FFAs、HOMA-IR和TNF-α水平均升高,P值均＜0.05,差异均有统计学意义;与模型组比较,治疗组血清ALT、AST、TC、TG、FFAs、HOMA-IR和TNF-α水平均降低,P值均＜0.05,差异有统计学意义.对照组肝组织phospho-c-Jun和cleaved caspase-3蛋白的表达分别为0.161±0.014和0.165±0.013,模型组分别为0.406±0.035和0.548±0.051,治疗组分别为0.226±0.021和0.Objective To observe the impact of the JNK inhibitor XG-102 in a diet-induced rat model of non-alcoholic steatohepatitis.Methods Forty-eight Sprague-Dawley male rats were subjected to a percutaneous superior mesenteric vein retention catheter operation and fed with a standard diet for 10days,after which the rats were randomly divided into the following three groups：normal control （NC） group;high-fat （HF） model group; XG-102 treatment group.The HF group was fed an HF diet and treated with 0.9% sodium chloride for 16 weeks.The XG-102 group was fed an HF diet for 16 weeks and simultaneously treated with XG-102 （1 mg/kg） once per day for 4 weeks.The levels of serum alanine aminotransferase （ALT）,aspartate aminotransferase （AST）,total cholesterol （TC）,triglyceride （TG）,homeostasis model of assessmentinsulin resistance （HOMA-IR） and tumor necrosis factor-alpha （TNFα） were measured.Liver histological changes were observed.The protein expressions of phospho-c-Jun and cleaved caspase-3 were detected by western blotting.Results Compared with the NC group,the HF group showed significantly higher levels of serum ALT,AST,TC,TG,HOMA-IR and TNFα （P 〈 0.05）.Compared with the HF group,the XG-102 group showed significantly lower levels of serum ALT,AST,TC,TG,HOMA-IR and TNFα （P 〈 0.05）.The HF group also showed significantly higher protein expression of phospho-c-Jun and cleaved caspase-3 than the NC group （P 〈 0.05） and the XG-102 group （P 〈 0.05）.Conclusion The JNK inhibitor XG-102 may ameliorate lipid metabolism,reduce insulin resistance,decrease liver injury and inhibit hepatocytes apoptosis.

关 键 词：炎症 C-JUN氨基末端激酶 胰岛素抵抗 凋亡 

分 类 号：R96[医药卫生—药理学]