有氧运动联合Ala-Gln对2型糖尿病大鼠心肌纤维化形成的干预作用及其机制研究
发布时间：2019-06-02 04:50
【摘要】：目的:(1)探讨有氧运动和Ala-Gln对T2DM心肌纤维化的干预作用和交互作用。(2)从心肌组织中氧化应激/NF-κB通路的变化,探讨运动训练和Ala-Gln干预T2DM心肌纤维化形成的生理机制。方法:选用雄性SD大鼠80只,随机抽取10只大鼠作为正常对照组(NC,n=10),平时不运动,标准饲料饲养。其余70只大鼠喂饲高脂膳食,6周后,在空腹状态下,注射小剂量的STZ(40mg/Kg体重),7天后,测试空腹血糖,当血糖达到11.1mmol/L为建模成功。再将建模成功的T2DM大鼠随机4组:糖尿病对照组(DMC,n=10)、糖尿病运动组(DME,n=10)、糖尿病+Ala-Gln 组(DMAG,n=10)和糖尿病+Ala-Gln+运动组(DMEAG,n=10),标准饲料饲养。DMC组平时不运动;运动锻炼采用60min无负重的游泳运动,每周6次;Ala-Gln在每次训练结束30min后灌服,补充剂量为1.5 g/Kg体重,每周6次。8周后,通过Elisa检测各组大鼠血清中空腹血糖(FBG)、胰岛素(INS)、C肽、胰高血糖素样肽-1(GLP-1)、心肌钙蛋白Ⅰ(cTnI)的含量和心肌组织核转录因子-κB(NF-κB)、转化生长因子-β1(TGF-β1)、肿瘤坏死因子-α(TNF-α)含量;通过RT-PCR检测心肌组织硫氧还蛋白还原酶(TR)、硫氧还蛋白(Trx)、Ⅰ、Ⅲ型胶原纤维mRNA的表达;通过硫代巴比妥酸法检测心肌组织丙二醛(MDA);通过分光光度计检测还原型谷胱甘肽(GSH)、氧化型谷胱甘肽(GSSG);以及分别观察心肌组织形态结构和超微结构。结果:(1)与NC组相比,DMC组FBG(P0.05)显著升高,血清GLP-1(P0.01)、C肽(P0.05)含量显著降低,INS含量有所增加,但无显著性差异(P0.05)。通过双因素方差分析,有氧运动可以使T2DM大鼠FBG极显著降低(P0.01),血清C肽含量极显著升高(P0.01),血清INS、GLP-1含量有所升高,但无显著性差异(P0.05);补充Ala-Gln可以使T2DM大鼠FBG(P0.05)含量显著降低,血清INS(P0.05)、GLP-1(P0.05)、C肽(P0.01)含量显著升高;有氧运动联合Ala-Gln对升高T2DM大鼠血清INS、C肽、GLP-1含量有显著交互作用(P0.05),但对降低FBG含量无显著交互作用(P0.05)。(2)与NC组相比,DMC组大鼠心肌组织Ⅰ型胶原纤维mRNA(P0.05)、Ⅲ型胶原纤维mRNA(P0.05)表达量显著升高。通过双因素方差分析,有氧运动使T2DM大鼠心肌组织Ⅰ、Ⅲ型胶原纤维mRNA表达显著降低(P0.05);补充Ala-Gln使心肌组织Ⅰ、Ⅲ型胶原纤维mRNA的表达显著降低(P0.05);有氧运动联合Ala-Gln对降低心肌组织Ⅰ、Ⅲ型胶原纤维mRNA表达无显著交互作用(P0.05)。与NC组相比,DMC组心肌细胞中肌原纤维排列紊乱,并有溶解现象,Z线扭曲;心肌细胞内线粒体大小不等,嵴模糊,数量减少。DME和DMAG组心肌细胞中肌原纤维排列较为整齐,Z线排列较整齐。线粒体数量多,形态大致正常。DMEAG组心肌细胞内肌原纤维排列整齐,肌丝结构清晰,Z线清晰而排列整齐,线粒体数量显著增多,嵴非常清楚。与此同时,与NC组相比,DMC组血清cTnI(P0.01)含量显著升高。通过双因素方差分析,有氧运动可使血清cTnI含量极显著降低(P0.01);补充Ala-Gln可以使血清cTnI(P0.01)含量显著降低;有氧运动联合Ala-Gln对降低血清cTnI含量无显著交互作用(P0.05)。(3)与NC组相比,DMC组心肌组织MDA(P0.05)、GSSG(P0.01)含量显著升高,GSH含量降低,但无显著性差异(P0.05),GSH/GSSG比值极显著降低(P0.01),TR、Trx mRNA的表达量显著降低(P0.05)。通过双因素方差分析可知,有氧运动使心肌组织MDA、GSSG含量显著降低(P0.05),GSH含量、GSH/GSSG比值和TrxmRNA表达升高,但无显著性差异(P0.05),而TR mRNA表达量显著升高(P0.05);补充Ala-Gln使心肌组织MDA(P0.01)、GSSG(P0.05)含量显著降低,GSH含量(P0.05)、GSH/GSSG比值(P0.01)显著升高,TR、Trx mRNA表达显著增加(P0.05)。有氧运动联合Ala-Gln对降低心肌组织MDA、GSSG含量和升高GSH含量、GSH/GSSG比值和TRmRNA表达均无显著的交互作用(P0.05),但对升高Trx mRNA表达有显著交互作用(P0.05)。(4)与NC组相比,DMC组心肌组织NF-κB、TGF-β1、TNF-α含量均显著升高(P0.05)。通过双因素方差分析,有氧运动使心肌组织NF-κB、TGF-β1、TNF-α含量显著降低(P0.01);补充 Ala-Gln 使 T2DM NF-κB(P0.01)、TGF-β1(P0.01)、TNF-α(P0.05)含量显著降低;有氧运动联合Ala-Gln对降低心肌组织NF-κB含量无显著交互作用(P0.05),但对降低TGF-β1(P0.01)和TNF-α(P0.05)含量有显著的交互作用。结论:(1)本研究所复制的T2DM大鼠模型是成功的,单纯有氧运动、Ala-Gln可以促进T2DM大鼠胰岛素的分泌,对控制T2DM大鼠的FBG具有显著的作用,而有氧运动联合Ala-Gln对降低T2DM大鼠的血糖更加有效。(2)T2DM大鼠在建模成功8周后,心肌组织就发生一定程度的纤维化,并引起心肌细胞发生一定程度的损伤。而有氧运动和补充Ala-Gln可以有效地抑制T2DM大鼠心肌纤维化的形成,且有氧运动联合Ala-Gln更加有效。(3)T2DM大鼠心肌组织中硫氧还蛋白系统功能的降低,引起心肌氧化应激,促进心肌组织中炎性因子的分泌,是T2DM心肌纤维化形成的重要机制;而有氧运动和补充Ala-Gln可提高T2DM心肌组织中硫氧还蛋白系统的功能,减少MDA的生成,从而减轻心肌组织中炎性因子的分泌,抑制T2DM心肌纤维化的发生和发展。
[Abstract]:Objective: (1) To study the effect and interaction of aerobic exercise and Ala-Gln on myocardial fibrosis in patients with T2DM. (2) The physiological mechanism of the formation of myocardial fibrosis in T2DM with exercise training and Ala-Gln was discussed. Methods:80 male SD rats were randomly selected as the normal control group (NC, n = 10). The remaining 70 rats were fed with a high-fat diet and, after 6 weeks, a small dose of STZ (40 mg/ kg body weight) was injected, and after 7 days, the fasting blood glucose was tested and the model was successful when the blood glucose reached 11.1 mmol/ L. The model was divided into four groups: the diabetic control group (DMC, n = 10), the diabetic group (DME, n = 10), the diabetes + Ala-Gln group (DMAG, n = 10) and the diabetes + Ala-Gln + exercise group (DMAGAG, n = 10), and the standard feed. The dmc group did not move normally; the exercise exercise had no weight-bearing swimming exercise for 60 minutes,6 times a week; the Ala-Gln was taken after 30 minutes at the end of each training, and the supplementary dose was 1.5 g/ Kg body weight,6 times a week. After 8 weeks, fasting blood glucose (FBG), insulin (INS), and C-peptide in the serum of each group were detected by Elisa. The content of Glucagon-like peptide-1 (GLP-1), the content of cardiac troponin I (cTnI) and the nuclear transcription factor-B (NF-EMAB), the transformation growth factor-1 (TGF-1), and the tumor necrosis factor-1 (TNF-1) content; The expression of thioredoxin reductase (TR), thioredoxin (Trx), 鈪，
本文编号：2490841
[Abstract]:Objective: (1) To study the effect and interaction of aerobic exercise and Ala-Gln on myocardial fibrosis in patients with T2DM. (2) The physiological mechanism of the formation of myocardial fibrosis in T2DM with exercise training and Ala-Gln was discussed. Methods:80 male SD rats were randomly selected as the normal control group (NC, n = 10). The remaining 70 rats were fed with a high-fat diet and, after 6 weeks, a small dose of STZ (40 mg/ kg body weight) was injected, and after 7 days, the fasting blood glucose was tested and the model was successful when the blood glucose reached 11.1 mmol/ L. The model was divided into four groups: the diabetic control group (DMC, n = 10), the diabetic group (DME, n = 10), the diabetes + Ala-Gln group (DMAG, n = 10) and the diabetes + Ala-Gln + exercise group (DMAGAG, n = 10), and the standard feed. The dmc group did not move normally; the exercise exercise had no weight-bearing swimming exercise for 60 minutes,6 times a week; the Ala-Gln was taken after 30 minutes at the end of each training, and the supplementary dose was 1.5 g/ Kg body weight,6 times a week. After 8 weeks, fasting blood glucose (FBG), insulin (INS), and C-peptide in the serum of each group were detected by Elisa. The content of Glucagon-like peptide-1 (GLP-1), the content of cardiac troponin I (cTnI) and the nuclear transcription factor-B (NF-EMAB), the transformation growth factor-1 (TGF-1), and the tumor necrosis factor-1 (TNF-1) content; The expression of thioredoxin reductase (TR), thioredoxin (Trx), 鈪，
本文编号：2490841
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