摘要
目的探讨钙调磷酸酶/活化T细胞因子（CaN/NFAT）信号通路在有氧运动诱导原发性高血压大鼠（SHR）肠系膜动脉血管平滑肌细胞电压依赖性钾通道（KV2.1）表达上调中的作用。方法选用3月龄雄性WKY和SHR大鼠各24只,随机分为WKY安静组和运动组（WKY-SED组、WKY-EX组）、SHR安静组和运动组（SHRSED组、SHR-EX组）。运动干预前和12周运动结束后分别测量大鼠安静状态下的心率和血压。分别采用免疫组化和Western blot检测KV2.1、CaN在肠系膜动脉的分布以及KV2.1、CaN、p-NFATc3、A型激酶锚定蛋白（AKAP150）和钙调蛋白（CaM）的蛋白表达。结果 （1）12周有氧运动后,与SHR-SED组相比,SHR-EX组心率、收缩压和平均动脉压均显著降低（P〈0.01）;与WKY-SED组相比,WKY-EX组收缩压显著降低（P〈0.05）。（2）与WKY-SED组相比,SHR-SED组KV2.1在肠系膜动脉的蛋白表达显著减少（P〈0.01）;与SHR-SED组相比,SHR-EX组KV2.1的蛋白表达显著增加（P〈0.01）。（3）与WKY-SED组相比,SHR-SED组CaN在肠系膜动脉的蛋白表达显著增加（P〈0.01）,p-NFATc3的蛋白表达显著减少（P〈0.01）;与SHR-SED组相比,SHR-EX组CaN的蛋白表达显著减少（P〈0.01）,p-NFATc3的蛋白表达显著增加（P〈0.01）。（4）与WKY-SED组相比,SHR-SED组的AKAP150蛋白表达显著增加（P〈0.01）;与SHR-SED组相比,SHR-EX组的AKAP150蛋白表达显著减少（P〈0.01）。（5）与WKY-SED组相比,SHR-SED组的CaM蛋白表达显著增加（P〈0.01）;与SHR-SED组相比,SHR-EX组的CaM蛋白表达显著减少（P〈0.01）;相比WKY-SED组,WKY-EX组CaM的蛋白表达量显著升高（P〈0.05）。结论钙调磷酸酶/活化T细胞核因子信号通路表达上调是高血压引起KV2.1通道功能下降的重要原因,有氧运动可以有效抑制这种作用,这可能是有氧运动缓解高血压及重塑血管功能的机制之一。
Aim To investigate the role of calcineurin/nuclear factor of activated T cells （CaN/NFAT） signaling pathway in aerobic exercise-induced increased expression of Kv2.1 channel in mesenteric artery vascular smooth muscle cell from spontaneously hypertensive rats （SHR）. Methods Male SHR and Wistar-Kyoto rats （WKY）, 12 weeks age, were randomly divided into control groups （WKY-SED, SHR-SED）, and exercise groups （WKY-EX, SHR-EX）. Exer- cise groups were subjected to a 12-week treadmill training protocol： 20 m/min, 60 min/day, 5 d/w. After 12 weeks, heart rate （HR） and blood pressure （BP） was acquired in each group. Immunocytochemistry was used to observe the dis- tribution and changing of Kv2.1 and CaN in mesenteric artery （MA）. Western blot was applied to examine the expression levels of Kv2.1, CaN, NFATc3, p-NFATc3, A-kinase anchoring protein （AKAP150） and calmodulin （CaM） protein in MA. Results （ 1 ） After 12 weeks of exercise, HR, systolic blood pressure （SBP） and mean blood pressure （MBP） in SHR-EX group was significantly lower than that in SHR-SED group （P〈0.01） ; SBP in WKY-EX group was lower than that in WKY-SED group （ P 〈 0. 05 ）. （ 2 ） The distribution and protein expression of Kv2. 1 in SHR-SED group was significantly lower than that in WKY-SED group （P〈0.01） ; Exercise training markedly increased the expression of Kv2.1 in SHR-EX group （P〈0.01）. （3） Compared with the WKY-SED group, the distribution and protein expression of CaN was significantly increased, but the protein expression of p-NFATc3 was significantly lower in SHR-SED group（P〈0.01 ） ; Exercise training markedly inhibited the distribution and expression of CaN and increased the expression of p-NFATc3 in SHR-EX group （P〈0.01）. （4） The protein expression of AKAP150 in SHR-SED group was significantly higher than that of WKY-SED group （ P〈0.01 ） ; aerobic exercise obviously decreased the upregulation protein expression of AKAP150 in hypertension�
作者
李珊珊
柏平
吴迎
李丽
曾凡星
石丽君
LI Shanshan;BAI Ping;WU Ying;LI Li;ZENG Fanxing;SHI Lijun(Key Laboratory of Physical Fitness and Exercise,Ministry of Education,Beijing Sport University,Beijing 100084,China)
出处
《中国动脉硬化杂志》
CAS
2018年第8期767-773,共7页
Chinese Journal of Arteriosclerosis
基金
国家自然科学基金项目(31771312)
北京市自然科学基金项目(5172023)
