小檗碱促进巨噬细胞M2型极化改善非酒精性脂肪性肝病肝脏炎症的机制  

Mechanism of Berberine Improving Liver Inflammation of Nonalcoholic Fatty Liver by Targeting Macrophages Polarization

作　　者：马丽 曹昕昱 孙永宁 MA Li;CAO Xinyu;SUN Yongning(Shanghai Municipal Hospital of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200071,China;Shaanxi Provincial Hospital of Traditional Chinese Medicine,Xi′an 710000,Shaanxi,China;Shaanxi Provincial People′s Hospital,Xi′an 710000,Shaanxi,China)

机构地区：[1]上海中医药大学附属上海市中医医院,上海200071 [2]陕西省中医医院,陕西西安710000 [3]陕西省人民医院,陕西西安710000

出　　处：《辽宁中医杂志》2024年第12期189-192,I0020,I0021,共6页Liaoning Journal of Traditional Chinese Medicine

摘　　要：目的探讨小檗碱通过促进巨噬细胞M2型极化改善高脂饮食诱导的非酒精性脂肪性肝病(nonalcoholic fatty liver,NAFLD)小鼠肝脏炎症的作用机制。方法通过给予8周龄c57bl/6小鼠高脂饮食16周建立NAFLD模型,对照组小鼠予以正常饮食。造模成功后分为NAFLD组和NAFLD+小檗碱给药组,小檗碱灌胃给药时间为8周(100 mg/kg体质量)。8周后通过油红染色观察肝脏脂滴情况;利用酶标仪评估小檗碱对血脂的影响;通过免疫组化染色评估小檗碱对肝脏代谢性炎症的影响;通过免疫荧光染色及激光共聚焦拍照分析小檗碱对肝脏巨噬细胞M2型极化标志物CD206的影响;提取小鼠肝脏纯化线粒体进行荧光探针染色,利用酶标仪检测小檗碱对肝脏线粒体活性氧(mitochondrial reactive oxygen species,mtROS)及锰超氧化物歧化酶(manganese superoxide dismutase,Mn-SOD)活力的影响。结果与对照组比较,NAFLD组小鼠肝脏脂肪沉积增加,空腹血糖、血清低密度脂蛋白胆固醇、总胆固醇及甘油三酯水平升高(P<0.05);肝脏炎症因子白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的表达升高(P<0.05),巨噬细胞CD206的表达降低(P<0.05);mtROS生成增加,Mn-SOD活力降低(P<0.05)。与NAFLD模型组比较,小檗碱给药能够改善以上变化(P<0.05)。结论小檗碱可能通过减少mtROS生成诱导巨噬细胞M2型极化改善NAFLD肝脏炎症状态。Objective To investigate the mechanism of berberine improving liver inflammation in nonalcoholic fatty liver(NAFLD)mice induced by high-fat diet by targeting the M2 type polarization of macrophages.Methods Eight-week-old c57bl/6 mice were fed high-fat diet for 16 weeks to establish the NAFLD model,and the mice in the control group were fed normal diet.After successful modeling,the mice were divided into NAFLD group and NAFLD supplemented with berberine group,and berberine was administered by gavage for 8 weeks(100 mg/kg body weight).After 8 weeks,the fat droplets in liver were observed by oil red staining.The effect of berberine on blood lipids was evaluated by enzyme marker.The effect of berberine on hepatic metabolic inflammation was evaluated by immunohistochemical staining.The effect of berberine on CD206,a marker of M2 type polarization,was analyzed by immunofluorescence staining and laser confocal photography in liver macrophages.The purified mitochondria from liver were extracted for fluorescent probe staining,and the effects of berberine on the activity of mitochondrial reactive oxygen species(mtROS)and manganese superoxide dismutase(Mn-SOD)in liver mitochondria were detected by enzyme marker.Results Compared with those of the control group,the liver fat deposition,the levels of fasting blood glucose,serum low density lipoprotein cholesterol,total cholesterol and triglyceride were raised in the NAFLD model group(P<0.05).The levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in liver were increased(P<0.05)and the expression of CD206 was reduced(P<0.05).The production of mtROS was increased(P<0.05)and the activity of Mn-SOD was decreased(P<0.05).Compared with the NAFLD group,NAFLD supplemented with berberine can improve the above changes(P<0.05).Conclusion Berberine may improve the inflammatory state with reducing the production of mtROS and inducing the M2 type polarization of macrophages in liver of NAFLD.

关 键 词：小檗碱 非酒精性脂肪肝 肝脏炎症 巨噬细胞极化 线粒体活性氧 

分 类 号：R285[医药卫生—中药学]