【摘要】 目的:观察妊娠期运动对自发性高血压大鼠（SHR）子代血压的影响,并探讨其血管平滑肌Ca_V1.2通道DNA甲基化机制。方法:WKY和SHR大鼠分别雌雄配种,孕鼠进行无负重游泳训练。分别检测3月龄（3M）和6月龄（6M）雄性子代体重、血压、肠系膜动脉反应性、血管平滑肌细胞Ca_V1.2通道全细胞电流、Ca_V1.2通道α₁C亚基蛋白和mRNA水平及其CACNA1C基因DNA甲基化情况和DNA甲基化转移酶DNMT1、DNMT3A和DNMT3B蛋白表达。结果:妊娠期运动显著降低高血压子代血压（P<0.05）、肠系膜动脉对Ca_V1.2通道阻断剂Nifedipine（P<0.05）的血管张力敏感性和肠系膜动脉平滑肌细胞Ca_V1.2通道的全细胞电流（P<0.05）、Ca_V1.2通道α1C亚基蛋白表达（P<0.05）和mRNA水平（P<0.01）。同时,CACNA1C基因启动子区的DNA甲基化（P<0.05）以及DNMT1、DNMT3A和DNMT3B蛋白表达均显著增加（P<0.01）。随年龄增加,妊娠期运动对6M高血压子代血压及CaV1.2通道功能的改善作用减弱。结论:妊娠期运动可显著降低高血压子代血压,Ca_V1.2通道α₁C亚基基因CACNA1C启动子区的DNA甲基化可能是其重要机制之一;随年龄增长,这一改善作用逐渐减弱。更多还原

【Abstract】 This research aims to observe the effects of exercise during pregnancy on the blood pressure of hypertensive rats’ offspring,and investigate the DNA methylation mechanism of the vascular smooth muscle Ca_V1.2 chan-nel. Research methods:male and female spontaneously hypertensive（SHR）rats and Wistar-Kyoto（WKY）ratswere mated respectively. The pregnant rats were subjected to swimming. The body weight,blood pressure,vascu-lar reactivity of mesenteric arteries,whole-cell Ca²⁺ current,Ca_V1.2 channel α₁C subunit protein and m RNA ex-pression,DNA methylation of the Ca_V1.2 channel α₁C subunit gene CACNA1C,DNA methyltransferase DNMT1,DNMT3A and DNMT3B protein expression of the 3-month-old（3 M）and 6-month-old（6 M）offspring were mea-sured. Results:Exercise during pregnancy significantly reduces the blood pressure（P<0.05）,sensitivity of thevascular tone to the Ca_V1.2 channel blocker Nifedipine in mesenteric artery（P<0.05）,the whole-cell current of Ca_V1.2 channels in mesenteric arterial smooth muscle cells（P<0.05）,the expressions of Ca_V1.2 channel α₁C sub-unit protein（P<0.05）and m RNA（P<0.01）of the SHR offspring. In this process,it was found that the DNA meth-ylation of the CACNA1C promoter region（P<0.05）and the protein expression of DNMT1（P<0.01）,DNMT3A（P<0.01）and DNMT3B（P<0.05）increased significantly. However,the effects of exercise during pregnancy onblood pressure and the function of the Ca_V1.2 channel were weaker for the 6 M SHR offspring than the 3 M SHR off-spring. Conclusions:Exercise during pregnancy reduces the blood pressure of SHR offspring. The DNA methyla-tion in the CACNA1C promoter region of the Ca_V1.2 channel α₁C subunit gene may be one of its important mecha-nisms;the improvement effects gradually weaken with age.更多还原