Cardiac fibrosis and down regulation of GLUT4 in experimental diabetic cardiomyopathy are ameliorated by chronic exposures to intermittent altitude.
Cardiac fibrosis and down regulation of GLUT4 in experimental diabetic cardiomyopathy are ameliorated by chronic exposures to intermittent altitude.
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DOI：
10.15171/jcvtr.2016.05
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发表时间：
2016
影响因子：
1.1
通讯作者：
Karimi P
中科院分区：
文献类型：
--
作者：
Faramoushi M;Amir Sasan R;Sari Sarraf V;Karimi P
简介：慢性间歇性低氧被认为是心血管健康的一种预适应状态，可诱导机体对低氧供应的抵抗。糖尿病心肌病导致心脏无法有效地血液循环，从而防止随后的组织损伤;本研究的目的是阐明慢性暴露于缺氧对实验性糖尿病心肌病中心脏纤维化和GLUT 4表达的影响。 方法：将30只大鼠随机分为3组：1.常氧对照组（NN，n = 10）。第二章：常氧糖尿病组（ND组，n = 10），先喂高脂饲料2周，然后腹腔注射链脲佐菌素（STZ）37 mg/kg;低氧糖尿病组（HD组，n = 10），慢性间歇性低氧（CIH）（海拔3400 m，14%氧气，连续8周）。采用比色法测定缺氧后大鼠空腹血糖（FBS）、甘油三酯（TG）、总胆固醇（TC）等血浆代谢指标。分别用免疫印迹法和Masson三色染色法检测左心室GLUT 4蛋白表达和胶原沉积。 结果：HD组与ND组比较，FBS、TG、TC显著降低（P < 0.05）。血液透析组动物的稳态模型评分（HOMA）较正常对照组明显降低（P < 0.05）。HD组红细胞压积和血红蛋白浓度较ND组明显增加（P < 0.05）。心脏湿重三组间比较有显著性差异（P < 0.05），HD组和ND组心脏湿重均低于NN组。与NN相比，ND的心肌纤维化明显更明显。低氧暴露8周可改善HD组的这种增加。间歇性低氧使HD组GLUT 4蛋白表达显著高于ND组（P < 0.05）。 结论：结果提示，CIH可能具有改善2型糖尿病（T2 D）患者血糖稳态和心脏组织结构损伤的作用。
Introduction: Chronic intermittent hypoxia is considered as a preconditioning status in cardiovascular health to inducing resistance to the low oxygen supply. Diabetic cardiomyopathy leads to inability of the heart to effective circulation of blood preventing of consequent tissue damages so; the aim of this study was elucidation of effect of chronic exposure to hypoxia on Cardiac fibrosis and expression of GLUT4 in experimental diabetic cardiomyopathy. Methods: A total number of 30 rats were randomly divided into three groups; 1: Normoxia control group (NN, n = 10). 2: Normoxia diabetic group (ND, n = 10) that took fat diet for 2 weeks then were injected by streptozotocin (37 mg/kg) and 3: Hypoxia diabetic group (HD, n = 10): that were exposed to chronic intermittent hypoxia (CIH) (altitude ≈3400 m, 14% oxygen for 8 weeks). After hypoxia challenge, plasma metabolic parameters including: fasting blood glucose (FBS), triglyceride (TG) and total cholesterol (TC) were measured by colorimetric assay. Cardiac expression of GLUT4 protein and cardiac collagen accumulation were determined in the excised left ventricle by western blotting, and Masson trichrome staining respectively. Results: Based on resultant data, FBS, TG and TC were significantly (P < 0.05) decreased in HD vs. ND. Homeostasis Model Assessment (HOMA) were also significantly attenuated after exposed to CIH in HD group compared to ND group (P < 0.05). Significant increase in packed cell volume and hemoglobin concentration was observed in HD group compared to ND group (P < 0.05). Comparison of heart wet weight between three groups showed a significant difference (P < 0.05) with lower amount in HD and ND versus NN. Myocardial fibrosis was significantly more pronounced in ND when compared to NN. Eight weeks exposure to hypoxia ameliorated this increase in HD group. Intermittent hypoxia significantly increased GLUT4 protein expression in HD compared to ND group (P < 0.05). Conclusion: Data suggested that CIH might potentiate to improve glucose homeostasis and cardiac tissue structural damages created in type 2 diabetes (T2D).