心梗大鼠持续和间歇运动干预的心肌血管新生相关miRNAs表征与EGFL7／miR126-PIK3R2／SPRED1通路激活的心脏保护效应  

Continuous and Interval Exercise Intervention on the Expression of Myocardial mi RNAs Related to Angiogenesis and Activitation of EGFL7/mi R126-PIK3R2/SPRED1 on Protecting the Hearts of MI Rats

作　　者：宋伟[1] 田振军[1] Shao-jun Du 

机构地区：[1]陕西师范大学体育学院暨运动生物学研究所,陕西西安710119 [2]马里兰大学,医学院生物化学与分子生物学系,美国巴尔的摩21202

出　　处：《体育科学》2017年第2期57-65,共9页China Sport Science

基　　金：国家自然科学基金资助项目(31371199);陕西师范大学中央高校基本业务费专项资金项目(GK201504001)

摘　　要：目的:探讨持续和间歇运动对心梗大鼠心脏血管新生相关mi RNAs表征及可能的效应机制。方法:3月龄雄性SD大鼠,随机分为假心梗组(S)、心梗组(MI)、心梗持续运动组(MCE)、心梗间歇运动组(MIE),每组10只。采用左脉前降支结扎制备心梗模型。MCE和MIE组术后1周进行跑台适应性训练(15 m/min,30 min/天×5天),之后MCE组以16 m/min(50%~60%O_(2max))速度持续运动64 min/天,5天/周×8周;MIE组以25 m/min×4 min(85%~90%O_(2max))和15 m/min×3 min(50%~60%O_(2max))速度依次交替运动49 min/天,5天/周×8周,训练结束后次日测定心功能。Masson染色观察分析心肌胶原容积分数(CFV),免疫组化观察心肌CD31和α-SMA表达,RT-q PCR检测心肌血管新生相关mi RNAs、egfl7、pik3r2和spred1表达,Western Blotting检测心肌PIK3R2、SPRED1和VEGF表达。结果:与S组比较,MI组心肌mi R-222表达显著上调,mi R-126表达显著下调,心肌CFV显著增加,心功能下降;与MI组比较,MIE组心肌mi R-17-5p、mi R-126表达均显著上调,MCE和MIE组CD31、α-SMA阳性颗粒显著增加,VEGF和egfl7 m RNA表达显著上调,且egfl7 m RNA与mi R-126表达呈高度正相关,PIK3R2、SPRED1蛋白及其m RNA表达均显著下调,心功能显著提升,且间歇运动优于持续运动。结论:间歇运动可显著上调心梗心脏mi R-126和mi R-17-5p表达,且mi R-126表达的变化率更大;持续和间歇运动显著激活心梗心脏EGFL7/mi R126-PIK3R2/SPRED1通路,抑制其下游靶蛋白PIK3R2/SPRED1表达,促进心脏梗死边缘区血管新生,产生心脏保护效应,且间歇运动的保护效应优于持续运动。Objectives： This study was carried out to investigate the continuous and interval exercise intervention on the expression of myocardial miRNAs related to angiogenesis and possible mechanism. Methods： 40 three-month-old male SD rats were randomly divided into four groups： sham-operated group（S）, myocardial infarction group （MI）, MI with continuous exercise group （MCE） and MI with interval exercise group （MIE）. MI model was induced by ligation of the left anterior descending （LAD） coronary artery. After five days＇ adaptive training （ 15m/min, 30min/d× 5d）, rats in MCE group performed continuous exercise for 64min/d, 5d/wkx8wk at the speed of 16m/min （50%-60% VO2max ）, and MIE intervals alternated between 4min at 25m/min （85%- 90% VO2max ） and 3min at 15m/min （50%-60% VO2max ） for 49min/d, 5d/wkx8wk. Cardiac function was measured the next day after 8wk training. CFV was analyzed through Masson＇ trichrome staining; CD31 and α-SMA were evaluated by immunohistochemistry. The expression of miRN.4s related to angiogenesis, egfl7, pik3r2, spredl were determined by RT-qPCR, while PIK3R2, SPRED1, VEGF were measured by Western Blotting. Results： Compared with S group, cardic function in MI was impaired with miR-222＇ upregulation and miR-126＇ downregulation; Compared with MI group, levels of miR-17-5p and miR-126 increased in MIE; meanwhile, in either MIE or MCE, positive granules of CD31 and a-SMA, VEGF, egfl7 mRNA were elevated and miR-126 was found to have a highly positive correlation with eg）q7 mRNA. in addition, the protein levels of PIK3R2, SPRED1 and their mRNA decreased, and rats in MIE group shows better performance than their counterparts in MCE group. Conclusions： Interval exercise training promotes an increase in the expression of miR-126 and miR-17-5p, and an even bigger change rate in miR- 126. Continuous and interval exercise could suppress the protein expression of PIK3R2/SPRED1 through the activation of EGFL7/miR126-PIK3R2/SPRED1, promote angiogenesis

关 键 词：心肌梗死 持续运动 间歇运动 MIR-126 PIK3R2/SPRED1 心肌血管新生 

分 类 号：G804.52[文化科学—运动人体科学]