木通皂苷D调节IL-6/STAT3轴对非酒精性脂肪性肝病大鼠的保肝作用研究  

Study on protective effect of Akebia saponin D on non-alcoholic fatty liver in rats by regulating IL-6/STAT3 axis

作　　者：张方洁 赵瑞娟[1,2] 王松[2] 张国民[1,2] 庞春淼 刘伟[1,2] 刘耀敏[1,2] ZHANG Fangjie;ZHAO Ruijuan;WANG Song;ZHANG Guomin;PANG Chunmiao;LIU Wei;LIU Yaomin(Department of Infectious Diseases,Affiliated Hospital of Chengde Medical College,Chengde 067000,China;Department of Thyroid Surgery,Affiliated Hospital of Chengde Medical College,Chengde 067000,China)

机构地区：[1]承德医学院附属医院感染性疾病科,承德067000 [2]承德医学院附属医院甲状腺外科,承德067000

出　　处：《中国免疫学杂志》2025年第4期822-827,共6页Chinese Journal of Immunology

基　　金：承德市科学技术研究与发展计划项目(202006A039)。

摘　　要：目的:探究木通皂苷D(ASD)调节IL-6/STAT3轴对非酒精性脂肪性肝病(NAFLD)大鼠的保肝作用。方法:将50只SD大鼠分为对照组、模型组、ASD低剂量组(ASD 20 mg/kg)、ASD高剂量组(ASD 40 mg/kg)和抑制剂组(ASD 40 mg/kg+IL-6/STAT3信号通路抑制剂LMT-283 mg/kg),每组10只。对照组大鼠喂食标准饲料,其他4组喂食高脂高糖饲料,所有大鼠均连续喂养6周,第7周起腹腔注射相应剂量药物,连续给药8周。所有大鼠称重,计算大鼠肝脏指数;全自动生化分析仪检测大鼠血清总胆固醇(TC)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、甘油三酯(TG)水平;HE染色观察大鼠肝脏组织病理变化;油红染色观察大鼠肝脏脂质积累情况;qRT-PCR检测大鼠肝脏组织IL-6、JAK1、STAT3表达;Western blot检测IL-6、JAK1、p-JAK1、STAT3、p-STAT3蛋白表达。结果:与对照组相比,模型组大鼠肝脏组织肝细胞肿胀,伴有较多气球样变,细胞质空泡化严重,肝小叶结构界限不清,伴有炎症细胞浸润,并可见明显的红色颗粒状脂滴占据大部分细胞质,大鼠体质量和肝脏指数、血清TC、ALT、AST、TG水平,以及肝脏组织IL-6、JAK1、STAT3 mRNA和IL-6、p-JAK1/JAK1、p-STAT3/STAT3蛋白表达明显升高(P<0.05);与模型组相比,ASD低、高剂量组大鼠肝小叶结构损伤减轻,肝细胞肿胀和空泡化减轻,肝组织脂滴积累明显减少,大鼠体质量和肝脏指数、血清TC、ALT、AST、TG水平明显降低(P<0.05),肝脏组织IL-6、JAK1、STAT3 mRNA和IL-6、p-JAK1/JAK1、p-STAT3/STAT3蛋白表达进一步升高(P<0.05);IL-6/STAT3信号通路抑制剂LMT-28减弱了ASD对NAFLD大鼠肝脏的保护作用。结论:ASD可通过激活IL-6/STAT3信号通路对NAFLD大鼠肝脏发挥保护作用。Objective:To investigate the protective effect of Akebia saponin D(ASD)on non-alcoholic fatty liver disease(NAFLD)in rats by regulating IL-6/STAT3 axis.Methods:Fifty SD rats were separated into control group,model group,low dose ASD group(ASD 20 mg/kg),high dose ASD group(ASD 40 mg/kg)and inhibitor group(ASD 40 mg/kg+IL-6/STAT3 signal pathway inhibitor LMT-283 mg/kg),with 10 rats in each group.Rats in control group were fed with standard diet,while the other four groups were fed with high fat and high sugar diet.All rats were fed for 6 consecutive weeks,and the corresponding dose of drugs was injected intraperitoneally from the 7th week,which were given drugs for 8 consecutive weeks.All rats were weighed to calculate liver index;levels of serum total cholesterol(TC),alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)were measured by automatic biochemical analyzer;HE staining was used to observe pathological changes of rats liver;oil red staining was used to observe lipid accumulation in rats liver;expressions of IL-6,JAK1,STAT3 in rats liver were detected by qRT-PCR;Western blot was used to detect expressions of IL-6,JAK1,p-JAK1,STAT3 and p-STAT3 proteins.Results:Compared with control group,hepatocytes in liver tissue of model group were swollen,accompanied by many ballooning changes,severe cytoplasmic vacuolization,the structure of hepatic lobule was unclear,and accompanied by inflammatory cell infiltration,and obvious red granular lipid droplets occupied most of the cytoplasm,body mass,liver index,levels of serum TC,ALT,AST,TG,expressions of IL-6,JAK1,STAT3 mRNAs,and IL-6,p-JAK1/JAK1,p-STAT3/STAT3 proteins in liver tissue of rats were obviously increased(P<0.05);compared with model group,damage of hepatic lobule structure in low and high doses ASD groups were reduced,swelling and vacuolization of liver cells were reduced,and accumulation of lipid droplets in liver tissue was obviously reduced.Body mass,liver index,levels of serum TC,ALT,AST and TG in rats were obviously decreased(P

关 键 词：木通皂苷D IL-6/STAT3轴 非酒精性脂肪肝大鼠 保肝 

分 类 号：R285.5[医药卫生—中药学]