糖肾方改善db/db小鼠脂代谢紊乱与巨噬细胞活化分型的实验研究  

Experimental study of Tangshen formulain improved lipid metabolism and phenotypic switch of macrophage in db / db mice

作　　者：孔勤[1,2] 张并璇[2] 张浩军[2] 严美花[2] 李平[1,2,3] 

机构地区：[1]中国医学科学院&北京协和医学院研究生院,北京100730 [2]中日友好临床医学研究所药物药理室,北京100029 [3]免疫炎性疾病北京市重点实验室,北京100029

出　　处：《中国中药杂志》2016年第9期1693-1698,共6页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81130066);国家国际科技合作专项项目(2011DFA31860);北京市科委计划项目(Z151100003815015)

摘　　要：肥胖、脂代谢紊乱及其相关代谢疾病,包括非酒精性脂肪肝(NAFLD)是公认的重要危险因素,患病人数逐年增加,已成为严重危害人类健康的慢性疾病之一。该研究主要探究糖肾方对C57BLKS/J db/db(db/db)小鼠脂代谢紊乱与巨噬细胞活化分型的作用及机制。8周龄雄性自发性糖尿病肥胖db/db小鼠与同源不发病db/m小鼠,随机分为正常对照组(db/m)、模型组(db/db)、糖肾方给药组(db/db+TSF),连续喂养12周后处死动物,留取组织标本备用。油红O染色检测肝脏脂滴沉积,免疫组织化学法检测肝脏巨噬细胞活化分型标记物CD68,F4/80的表达变化;荧光定量PCR法检测白色脂肪组织巨噬细胞活化标记物Mrc1,Arg1,TNF-α等m RNA表达。研究发现与正常对照组相比,模型组小鼠肝组织脂质沉积增多,TSF干预后脂质沉积显著减少;db/db小鼠肝脏组织CD68和F4/80的表达增加,TSF干预后可显著抑制其表达水平;此外,与正常对照组相比,db/db小鼠白色脂肪组织巨噬细胞活化标记物Mrc1,Arg1和TNF-αm RNA表达增加,TSF干预后TNF-α显著下降,但Mrc1,Arg1无显著差异。结果表明中药糖肾方可减轻db/db小鼠肝脏脂肪变,改善血脂异常,其机制可能与其调节巨噬细胞活化有关。Obesity and its associated metabolic disorders,including non-alcoholic fatty liver disease（ NAFLD）,have become major chronic diseases threatening public health. NAFLD is a chronic liver disorder that is strongly associated with type 2 diabetes and obesity. In this study,we investigated the effects and mechanism of Tangshen formula（ TSF） on hepatic dyslipidemia and phenotypic switch of macrophage in db / db mice. Eight-week-old male C57 BLKS / J db / m control and db / db mice were divided into 3 groups（ namely db /m,db / db,db / db ＋ TSF）,and fed with TSF or distilled water for 12 weeks. It was found that after treatment with TSF,the triglycerides accumulation in db / db mice was decreased on the basis of oil red O staining with cryosections of liver tissues. And protein expressions of macrophage activation markers CD68 and F4 /80 were decreased according to immunohistochemical analysis of hepatic sections.The m RNA level of TNF-α（ M1 marker） was significantly decreased by TSF in db / db mice,but with no significant difference in Mrc1 and Arg1（ M2 marker）. According to the results,TSF attenuated hepatic steatosis and relieved dyslipidemia,its mechanism may be correlated with the regulation of macrophage activation and phenotypic switch.

关 键 词：糖肾方 非酒精性脂肪肝 肝脏脂肪变 巨噬细胞活化 

分 类 号：R285.5[医药卫生—中药学]