间歇有氧运动激活心梗大鼠肾脏miR-21/TLR4/NF-κB通路抑制肾脏炎症反应
Aerobic Interval Training Activates the Renal miR-21/TLR4/NF-κB Signaling Pathway and Inhibits Renal Inflammation in Rat with Myocardial Infarction

摘要：目的：探讨间歇有氧运动激活心梗 (MI) 大鼠肾脏miR-21及下游通路TLR4/NF-κB 抑制肾脏炎症反应的作用。方法：3月龄雄性SD大鼠40只，随机选取12只为假手术组 (Sham)，Sham组大鼠实施假手术； 28只大鼠结扎心脏左冠状动脉前降支 (LAD)，构建MI模型，术后存活24只，随机分为心肌梗死组 (MI)和心梗＋间歇有氧运动组 (ME)，每组12只。ME 组术后1周进行跑台适应性训练：15 m/min，30 min/d，共5 d。正式训练以10 m/min速度运动10 min，之后以25 m/min×7 min和15 m/min×3min依次交替进行，最后以10 m/min速度运动1 min，运动总时间为60 min。以上训练方案每周5 d，训练至8 周结束。训练结束后次日腹腔麻醉，血流动力学测定各组大鼠心功能，ELISA法测定尿液NAG和KIM-1和肾脏IL-6和IL-10表达，RT-qPCR 检测肾脏miR-21表达，Western blot 检测肾脏TLR4和磷酸化NF-κBp65 蛋白表达。结果：心梗大鼠肾脏功能受损，肾脏炎症因子IL-6增多，抗炎因子IL-10减少，尿液NAG和KIM-1水平升高。间歇运动可显著改善心梗大鼠肾脏功能，降低肾脏IL-6水平，增加IL-10水平，降低尿液NAG和KIM-1水平，上调肾脏miR-21的表达水平，抑制TLR4和NF-κB磷酸化水平。结论：间歇运动可显著增加心梗大鼠肾脏局部miR-21表达，抑制其下游TLR4/NF-κB信号通路，抑制肾脏炎症反应，改善肾功能。
Abstract: Objective: The purpose of this study was to explore the effect of aerobic interval training on renal miR-21, TLR4/NF-κB and renal inflammation in rats with myocardial infarction. Methods: Forty male 3-month old Sprague-Dawley rats were included in this study, 12 of them were in Sham-operated group (Sham), 28 were established MI model by the surgery of ligation of left anterior descending coronary artery (LAD), and then 24 of the 28 survived and divided into MI group and MI plus exercise group (ME) (n=12). One weeks after surgery, ME rats performed 5 days adaptive training (15 m/min, 30 min/d), and then performed 8 weeks training (training program: 10 min 10m/min, 5 intervals alternated between 7 min at 25m/min and 3 min at 15m/min, 1min 10m/min, 60 min in total, 5 times/week). The samples were collected the day after the last training. The cardiac function was evaluated by hemodynamics, the levels of urine NAG and KIM-1 and renal IL-6 and IL-10 were assessed by ELISA, the expression level of renal miR-21 was examined by RT-qPCR, and the expressions of renal TLR4 and p-NF-κBp65 were tested by Western blot. Results: The MI rats’ renal function was impaired, IL-6 in kidney was increased, IL-10 was decreased, and the levels of NAG and KIM-1 in urine were increased. Interval training improved the renal function of MI rats, decreased IL-6, increased IL-10, decreased the levels of NAG and KIM-1 in urine, and increased the expression of miR-21, inhibited expressions of TLR4 and p-NF-κBp65. Conclusion: Interval training can improve the expression of miR-21, inhibit TLR4/NF-κB signaling pathway, inhibit renal inflammation, and improve renal function