津力达对高脂诱导的胰岛素抵抗ApoE^(-/-)小鼠骨骼肌胆固醇相关基因的影响

Effect of Jinlida on cholesterol-related genes in skeletal muscle in fat-induced insulin resistance ApoE^(-/-) mice

目的探讨津力达对高脂诱导的胰岛素抵抗ApoE-/-小鼠骨骼肌胆固醇相关基因的影响。方法 10只♂C57BL/6J小鼠设为正常组(NF);50只♂ApoE-/-小鼠高脂喂养16周后分为模型组(HF)、罗格列酮组(LGLT)、津力达低剂量组(JLDL,0.95 g·kg-1·d-1)、津力达中剂量组(JLDM,1.9 g·kg-1·d-1)、津力达高剂量组(JLDH,3.8 g·kg-1·d-1),开始灌胃给药,连续8周。采用油红O染色观察小鼠骨骼肌的脂肪蓄积情况;采用实时荧光定量反转录PCR(RT-PCR)和蛋白质印迹法(Western blot)测定小鼠骨骼肌胰岛素受体(INSR)、胰岛素受体底物-1(IRS-1)、低密度脂蛋白受体(LDLR)、胆固醇敏感器(SCAP)mRNA和蛋白表达。结果与NF组相比,HF组小鼠空腹血糖(FBG)、胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)均明显升高,高密度脂蛋白(HDL-C)明显降低(P<0.05);与HF组相比,津力达组能够不同程度降低小鼠的FBG、TC、TG和LDL-C,升高HDL-C(P<0.05);津力达(Jinlida,JLD)能够下调空腹血清胰岛素(FINS)水平,提高胰岛素敏感指数(ISI)(P<0.05);津力达能够明显改善小鼠的骨骼肌脂肪蓄积;与NF组比较,HF组骨骼肌INSR、IRS-1、LDLR mRNA和蛋白水平均明显下降(P<0.05),SCAP mRNA和蛋白水平明显升高(P<0.05);与HF组比较,津力达各组能够不同程度地上调INSR、IRS-1、LDLR mRNA和蛋白水平(P<0.05),下调SCAP mRNA和蛋白水平(P<0.05)。结论津力达能够通过调节骨骼肌胆固醇相关基因表达,改善高脂诱导的ApoE-/-小鼠的胰岛素抵抗。

Aim To investigate the effect of Jinlida on cholesterol-related genes in skeletal muscle in fat-in-duced insulin resistance ApoE-/ - mice. Methods Ten male C57 BL/6 J mice were selected as normal group （ NF ）;50 male ApoE-/ - mice with a high-fat feeding after 16 weeks （ HF） were divided into model group, rosiglitazone （ LGLT ） , Jinlida low dose group （ JLDL, 0. 95 g · kg-1 · d-1 ） , Jinlida medium dose group （ JLDM, 1. 9 g·kg-1 ·d-1 ） , Jinlida high dose group （JLDH, 3. 8 g·kg-1·d-1）, which were per-formed intragastric administration for 8 weeks. Oil red O staining of mouse skeletal muscle was used for fat ac-cumulation. Insulin receptor （ INSR） , insulin receptor body substrate-1 （ IRS-1 ） , low-density lipoprotein re-ceptor （ LDLR ） , cholesterol sensor （ SCAP ） mRNA and protein expression in mouse skeletal muscle were measured by quantitative reverse transcription PCR （ RT-PCR ） and Western blot. Results Compared with NF group, fasting blood glucose （ FBG） , choles-terol （ TC ） , triglyceride （ TG ） and low density lipo-protein cholesterol （ LDL-C ） of HF mice were signifi-cantly elevated, while high-density lipoprotein （ HDL-C ） significantly decreased （ P 〈 0. 05 ） . Compared with HF group, Jinlida group could reduce to varying degrees FBG, TC, TG and LDL-C in mice, and in-crease HDL-C （ P 〈0. 05 ） . Jinlida could downgrade fasting serum insulin （ FINS ） level, and improve the insulin sensitive index （ ISI ） （ P 〈 0. 05 ） . Jinlida could obviously improve skeletal muscle fat accumula-tion of mice. Compared with NF group, skeletal mus-cle INSR, IRS-1, LDLR mRNA and protein levels of HF group were significantly decreased （ P 〈0. 05 ） , while SCAP mRNA and protein level increased signifi-cantly （P〈0. 05）. Compared with HF group, Jinlida could increase to varying degrees INSR, IRS-1, LDLR mRNA and protein levels （ P 〈 0. 05 ） , and lower SCAP mRNA and protein levels （ P〈0. 05 ） . Conclu-sion Jinlida can alleviate fat-induced insulin resist-ance in ApoE-/ - mice through regulation of cholester-ol-related gene expression.