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目的:探讨缺氧诱导因子-lα(HIF-1α)对糖尿病心肌病大鼠心肌超微结构、血管生成的影响。方法:将24只雄性Wister大鼠随机分为对照组和实验组。两组动物均采用高糖高脂饲料喂养,在喂养6周后给予链脲佐菌素腹腔注射建立糖尿病心肌病模型。分别于第8周、第10周,给予对照组大鼠尾静脉注射100μg空载体质粒(pShuttle),给予实验组大鼠尾静脉注射100μg重组HIF-1α过表达质粒(pShuttle-HIF-1α)。每2周采集大鼠静脉血,检测血糖、血脂。第12周时处死动物,留取血液和心肌组织。采用透射电镜观察心肌细胞超微结构,苏木素-伊红染色检测心肌血管密度,Western blot检测心肌组织中HIF-1α和血管内皮生长因子(VEGF)的蛋白表达水平。结果:与对照组相比,实验组大鼠心肌组织中HIF-1α和VEGF表达明显增高,心肌毛细血管数目明显增多,心肌细胞超微结构损伤明显减轻。结论:HIF-1α可能通过诱导VEGF表达,减轻糖尿病心肌病大鼠心肌超微结构损伤并促进心肌血管形成。
Objective: To investigate the effects of hypoxia inducible factor-1α (HIF-1α) on myocardial ultrastructure and angiogenesis in diabetic cardiomyopathy rats. Methods: 24 male Wister rats were randomly divided into control group and experimental group. Animals in both groups were fed with high-sugar and high-fat diet, and streptozotocin was given intraperitoneally to establish diabetic cardiomyopathy model 6 weeks after feeding. At week 8 and week 10, rats in control group were injected with 100 μg of pShuttle plasmid via the tail vein and 100 μg of recombinant HIF-1α overexpression plasmid (pShuttle-HIF-1α) was injected into tail vein of experimental group. Rat venous blood was collected every 2 weeks and blood glucose and blood lipids were measured. Animals were sacrificed on week 12, and blood and myocardial tissue were collected. The ultrastructure of myocardial cells was observed by transmission electron microscopy, the myocardial vascular density was detected by hematoxylin-eosin staining, and the protein expression of HIF-1α and VEGF in myocardium was detected by Western blot. Results: Compared with the control group, the expression of HIF-1α and VEGF in the experimental group was significantly increased, the number of myocardial capillaries was significantly increased, and the myocardial ultrastructure damage was significantly reduced. Conclusion: HIF-1α may reduce myocardial ultrastructure damage and promote myocardial angiogenesis in diabetic cardiomyopathy rats by inducing VEGF expression.