CsA及VIVIT对自发性高血压大鼠T淋巴细胞CaN/NFAT信号通路的影响

Influence of CsA and VIVIT on CaN/NFAT signaling pathway of T lymphocytes in spontaneously hypertensive rat

目的:研究环孢菌素A(CsA)及钙调神经磷酸酶(CaN)/活化T细胞核因子(NFAT)信号通路抑制剂VIVIT(Valine isoleucine valine isoleucine threonine,整体形式的寡肽缬氨酸-异亮氨酸-缬氨酸-异亮氨酸-苏氨酸)对自发性高血压大鼠(SHR)T淋巴细胞CaN/NFAT信号通路的影响。方法:40只12周龄雄性SHR被随机均分SHR组、安慰剂(PLA)组(SHR组基础上加用PLA)、CsA组(SHR组基础上加用CsA)与VIVIT组(SHR组基础上加用VIVIT),另选择10只同龄健康雄性魏-凯氏大鼠(WKY)作为WKY组。比较各组T淋巴细胞钙调磷酸酶催化亚基A基因(protein phosphatase 3 catalytic A,PPP3CA)蛋白及NFAT2蛋白积分光密度量。结果:与WKY组比较,SHR组、PLA组PPP3CA[7461(11054,17140)比14222(8951,12323)比11716(10219,23755)]、NFAT2蛋白积分光密度量[7715(5204,10224)比24759(16722,32796)比18441(13947,22934)]显著升高;与SHR组、PLA组比较,CsA组、VIVIT组PPP3CA[14222(8951,12323),11716(10219,23755)比6255(11683,19635),7474(5949,10066)]、NFAT2蛋白积分光密度量[24759(16722,32796),18441(13947,22934)比9300(5388,13210),10146(5949,10066)]显著降低,P<0.05或<0.01。结论:自发性高血压大鼠T细胞CaN/NFAT信号通路活性显著升高,CsA和VIVIT对自发性高血压大鼠T细胞CaN/NFAT信号通路有显著抑制作用。

Objective:To study influence of cyclospoline A(CsA)and calcineurin(CaN)/nuclear factor of activated T cells(NFAT)signaling pathway inhibitor VIVIT on CaN/NFAT signaling pathway of T lymphocytes in spontaneously hypertensive rat(SHR).Methods:A total of 4012-week-old male SHRs were randomly and equally divided into SHR group,placebo(PLA)group(received PLA based on SHR group),CsA group(received CsA based on SHR group)and VIVIT group(received VIVIT based on SHR group).Another 1012-week-old healthy male Wister-Kyoto rats(WKY)were regarded as WKY group.Integral optical density of T lymphocyte protein phosphatase 3 catalytic A(PPP3 CA)protein and NFAT2 protein were compared among all groups.Results:Compared with WKY group,there were significant rise in integral optical density of PPP3 CA protein[7461(11054,17140)vs.14222(8951,12323)vs.11716(10219,23755)]and NFAT2 protein[7715(5204,10224)vs.24759(16722,32796)vs.18441(13947,22934)]in SHR group and PLA group;compared with SHR group and PLA group,there were significant reductions in integral optical density of PPP3 CA protein[14222(8951,12323),11716(10219,23755)vs.6255(11683,19635),7474(5949,10066)]and NFAT2 protein[24759(16722,32796),18441(13947,22934)vs.9300(5388,13210),10146(5949,10066)]in CsA group and VIVIT group,P<0.05 or<0.01.Conclusion:Activity of CaN/NFAT signaling pathway of T lymphocytes significantly rise in SHR,and CsA and VIVIT possess significantly inhibitory effects on CaN/NFAT signaling pathway of T lymphocytes in SHR.