【摘要】 目的:比较间歇低氧和间歇运动干预对心梗大鼠心肌HIF-1α、miR-126表达及血管新生的影响,并对其相互之间的关系进行探讨。方法:雄性SD大鼠随机分为假心梗组(S)、心梗组(MI)、心梗+间歇低氧组(MIH)、心梗+间歇运动组(MIE)。人脐静脉内皮细胞(HUVECs)给予不同时间的低氧处理。左冠状动脉前降支结扎制备心肌梗死模型。4周正式训练结束次日测定心功能、心脏质量、胫骨长度、计算心胫比(HW/TL)。Masson染色观察分析心肌胶原容积分数(CFV),免疫荧光染色进行血管新生观察,RT-qPCR检测心肌和HUVECs miR-126表达,Western Blotting检测心肌和HUVECs HIF-1α、Ets-2、VEGF表达。结果:与S组比较,MI组HW/TL显著升高,心肌HIF-1α、VEGF表达显著上调,miR-126表达显著下调,心肌CFV显著增加,心功能下降;与MI组比较,MIH组HW/TL显著降低,MIE组HW/TL显著升高,两组心肌HIF-1α、VEGF和miR-126表达均显著上调,心肌CFV显著降低,PCNA+/vWF+阳性颗粒增加,心功能显著提升,且IE效果显著优于IH。离体实验发现,随着低氧时间延长,HIF-1α、miR-126表达先上升后下降,变化趋势高度一致。结论:间歇低氧和间歇运动可能通过HIF-1α上调心梗心肌miR-126表达,促进心肌血管新生,改善心功能,且间歇运动产生的效果要优于间歇低氧。提示,对于临床上不适宜进行运动康复治疗的缺血性心脏病患者,间歇低氧可以作为一种很好的替代和补充。更多还原

【Abstract】 Objective: To compare the effects of intermittent hypoxia(IH) and interval exercise(IE) on the expression of myocardial HIF-1α, miR-126 and myocardial angiogenesis and analyze the relationship among them. Methods: Male SD rats were randomly divided into 4 groups:Sham-operated group(S), myocardial infarction group(MI), MI with interval hypoxia group(MIH) and MI with interval exercise group(MIE). Human umbilical vein endothelial cells(HUVECs) were treated for various durations under hypoxia. MI model was induced by ligation of the left anterior descending(LAD) coronary artery. Cardiac function, cardiac weight, and tibia length was measured the next day after 4 week formal training to calculate heart to tibial ratio(HW/TL). CFV was analyzed through Masson’ trichrome staining; myocardial angiogenesis were evaluated by immunohistochemistry. The expression of HUVECs miR-126 were determined by RT-qPCR, while HUVECs HIF-1α、 Ets-2 and VEGF were measured by Western Blotting. Results: Compared with S group, HW/TL was significantly increased, the expression of HIF-1α and VEGF was significantly increased, the expression of miR-126 was significantly decreased, CFV was significantly increased, and cardiac function was decreased in MI group;compared with the MI group, the HW/TL in the MIH group was significantly decreased, and the HW/TL in the MIE group was significantly increased. The expressions of HIF-1α, VEGF and miR-126 in the myocardium of the two groups were significantly increased, the CFV in the myocardium was significantly decreased, the PCNA+/v WF+positive particles were increased,and the cardiac function was significantly improved, and the effect of IE was significantly better than that of IH. In vitro experiments showed that with the prolongation of hypoxia time, the expressions of HIF-1α and miR-126 increased first and then decreased, with a highly consistent trend. Conclusions: IH and IE may upregulate the expression of miR-126 through HIF-1α,which contribute to myocardial angiogenesis and cardiac function in MI hearts, with IE outperforming IH. Implications: IH approach could present an alternative therapy to ischemic heart patients who can not resort to exercise treatment.更多还原