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

孔勤 张并璇 张浩军 严美花 李平

[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。該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，TNFα等mRNA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TNFα mRNA表达增加，TSF干预后TNFα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。

[关键词]糖肾方；非酒精性脂肪肝；肝脏脂肪变；巨噬细胞活化

[Abstract]Obesity and its associated metabolic disorders， including nonalcoholic 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 Eightweekold male C57BLKS/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 mRNA level of TNFα （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

[Key words]Tangshen formula； nonalcoholic fatty liver disease（NAFLD）； hepatic steatosis； macrophage activation

doi：10.4268/cjcmm20160920

非酒精性脂肪肝病（nonalcoholic fatty liver disease， NAFLD）是一类以甘油三酯为主的脂质在肝脏组织中异常蓄积为病理改变的疾病（除饮酒和其他已明确的肝损伤因素），是最为常见的一类慢性肝脏疾病，目前我国患病率约为15%～30%[1]。其发生发展包括单纯性脂肪肝、脂肪性肝炎、肝硬化和肝癌4个阶段。……