增龄和高血压经PI3K/Akt和MAPK信号通路间平衡介导调控血管平滑肌细胞的表型转换  

Aging and hypertension mediate the phenotypic switching of vascular smooth muscle cells through the balance between PI3K/Akt and MAPK signaling pathways

作　　者：张琳[1] 廖静雯[1] 吴迎[1] 曾凡星[1] 石丽君[1] ZHANG Lin LIAO Jing-Wen WU Ying ZENG Fan-Xing SHI Li-Jun(Department of Exercise and Physical Health, Beijing Sport University, Beijing 100084, Chlna)

机构地区：[1]北京体育大学运动与体质健康实验室,北京市100084

出　　处：《中国动脉硬化杂志》2017年第9期865-873,共9页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金项目(31371201);国家体育总局全民健身领域课题(2015B035)

摘　　要：目的探究增龄和高血压对胸主动脉血管平滑肌细胞(VSMC)表型转换的影响及磷脂酰肌醇激酶(PI3K/Akt)和丝裂原活化蛋白激酶(MAPK)信号通路对VSMC表型的调控。方法选取1、3、9、16月龄的雄性Wistar Kyoto大鼠(WKY)和自发性高血压大鼠(SHR)各12只,尾动脉无创测定血压,取各组大鼠的胸主动脉进行实验。HE染色测量胸主动脉的管壁厚度;免疫组织化学染色检测VSMC表型标志蛋白α平滑肌肌动蛋白(α-SMactin)、调宁蛋白、骨桥蛋白(OPN)的表达和分布;Western blot检测VSMC表型标志蛋白α-SM-actin、调宁蛋白、OPN及信号蛋白p-Akt、内皮型一氧化氮合酶(eNOS)、p-42/44ERK、p-p38MAPK的表达量。结果 HE染色结果显示,增龄导致管壁厚度增加,且在9月龄时WKY和SHR出现显著差异(P<0.01)。免疫组织化学染色和Western blot结果表明,3月龄后,WKY和SHR的α-SM-actin、调宁蛋白表达量随月龄增加出现下调,而OPN出现上调;p-Akt、eNOS的蛋白表达量随月龄增加逐渐下调,p-42/44ERK、p-p38MAPK蛋白表达量随月龄增长逐渐上调,且3月龄时两组已有显著差异(P<0.01)。结论增龄和高血压均导致大鼠胸主动脉VSMC收缩表型标志蛋白α-SM-actin、调宁蛋白的表达下调,合成表型标志蛋白OPN的表达上调,二者的交互作用更显著。VSMC的表型转换可能是通过PI3K/Akt和MAPK信号通路间的平衡作用进行调控的。Ahn To explore the effects of aging and hypertension on phenotypic switching of thoracic aortic vascular smooth muscle cell （VSMC） and regulation of VSMC phenotype by phosphatidylinositol 3-kinase （PI3K/Akt） and mitogen-acti- vated protein kinase （MAPK） signaling pathway. Methods Male Wistar Kyoto rats （WKY） and spontaneously hypertensive rats （SHR） were studied at 1, 3, 9, 16 months of age, and each group had 12 rats. Blood pressure was noninvasively measured in the caudal artery. The thoracic aorta of rats in each group was taken for the experiment. HE staining was used to measure the wall thickness of the thoracic aorta. The expression and distribution of VSMC phenotype marker proteins a-smooth muscle- actin （a-SM-actin）, calponin and osteopontin （OPN） were detected by immunohistochemical staining. Western blot was used to detect the expression of VSMC phenotype marker protein α-SM-actin, calponin, OPN, and signal proteins p-Akt, endothelial nitric oxide synthase （eNOS）, p-42/44ERK and p-p38MAPK. Results HE staining showed that aging resulted in an in- crease in the thickness of vascular wall, and at 9 months old, there was a significant difference between WKY and SHR （P〈 0.01） staining and Western blot showed that after 3 months old, the expressions of α-SM-actin and cal- ponin in WKY and SHR decreased with the increase of age, while OPN increased; The expressions of p-Akt and eNOS proteins gradually decreased with the increase of age, and the expressions of p-42/44ERK and p-p38MAPK proteins increased gradually with the increase of age; At 3 months old, there was significant difference between the two groups （P〈0.01）. Conclusion Aging and hypertension all contribute to the decreases in expressions of VSMC contractile phenotype marker proteins oL-SM-actin and calponin, and the increase in the expression of VSMC synthetic phenotypic marker protein OPN in rat thoracic aorta. The interaction between aging and hypertension is more significant. The phenotypic switching

关 键 词：增龄 高血压 血管平滑肌细胞 表型转换 PI3K/AKT通路 MAPK通路 

分 类 号：R363[医药卫生—病理学]