脂联素通过TGF-β_1/Smads信号通路对2型糖尿病大鼠心肌病变的保护作用
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摘要
目的观察脂联素(APN)对2型糖尿病(T2DM)模型大鼠心肌细胞转化生长因子β_1/信号传导蛋白(TGF-β_1/Smads)通路的干扰,揭示2型糖尿病心肌病心肌纤维化的发病机制。方法分为普通对照组(NC,20只)、模型组(70只)。模型组采用高脂高糖饮食加腹腔注射小剂量链脲佐菌素(STZ)建立T2DM模型。将造模成功的大鼠继续喂养12周后分为脂联素注射组(DA组,30只)、2型糖尿病心肌病组(DCM组,31只)。脂联素注射组大鼠腹腔注射APN 10μg/kg,2型糖尿病心肌病组和正常对照组大鼠注射同等剂量生理盐水。3组分别于注射4周末、8周末、12周末取大鼠开始测验。心脏彩超测量心脏功能,RT-PCR测定相关因子mRNA含量,Western blot法检测相关因子蛋白表达。结果在各时间段中,与NC组相比,DCM组大鼠心重指数增加,心功能明显下降,脂联素干预后心功能好转;Western blot结果显示,各时间段中,与NC组相比,DCM组心肌组织TGF-β_1、Smad3表达增加,脂联素干预后DA组二者表达较DCM组减少,且呈时间依赖性;2型糖尿病心肌病组Smad7表达明显比普通对照组降低,球形脂联素注射后表达明显比2型糖尿病心肌病组升高,且呈时间依赖性增加。结论 APN可能通过抑制TGF-β_1/Smads信号通路,改善心功能,对2型糖尿病大鼠心肌病变有保护作用。
引文
[1] 张晶,李兴,魏立静,等.脂联素对高糖环境下心肌细胞中 TGF β1/Smads通路的影响[J].中西医结合心脑血管病杂志,2013,11(4):458-460.
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[2] TSUTSUI H,KINUGAWA S,MATSUSHINMA S,et al.Oxidative stress in cardiac and skeletal muscle dysfunction associated with diabetes mellitus[J].J Clin Biochem Nutr,2011,48(1):68-71.
[3] RYDEN L,GRANT P J,ANKER S D,et al.ESC guidelines on diabetes,pre-diabetes,and cardiovascular disease developed in collaboration with the EASD-summary.Task force on diabetes,pre-diabetes,and cardiovascular diseases of the European Society of Cardiology(ESC);European Association for the Study of diabetes(EASD)[J].Diab Vasc Dis Res,2014,11(3):133-173.
[4] ASBUN J,VILLARREAL F J.The pathogenesis of myocardial fibrosis in the setting of diabetic cardiomyopathy[J].Journal of the American College of Cardiology,2006,47:693-700.
[5] FUJITA K,MAEDA N,SONODA M,et al.Adiponectin protects against angiotensin Ⅱ-induced cardiac fibrosis through activation of PPAR-alpha[J].Arterioscler Thromb Vasc Biol,2008,28:863-870.
[6] KONISHI M,HARAGUCHI G,OHIGASHI H,et al.Adiponectin protects against doxorubic-ininduced cardiomyopathy by anti-apoptotic effects through AMPK up-regulation[J].Cardiovase Res,2011,89:309-319.
[7] QI G M,JIA L,LI Y L,et al.Adiponectin suppresses angiotensin Ⅱ-induced inflammation and cardiac fibrosis through activation of macrophage autophagy[J].Endocrinology,2014,155(6):2254-2265.
[8] MOTOSHIMA H,WU X,MAHADEV K,et al.Adiponectin suppresses proliferation and superoxide generation and enhances eNOS activity in endothelial cells treated with oxidized LDL[J].Biochem Biophys Res Commun,2004,315:264-271.
[9] 王春燕,张伟,周义文,等.脂联素通过抗氧化应激降低糖尿病心肌病心肌纤维化[J].国际检验医学杂志,2010,31(8):780-782.