淋巴细胞连接蛋白调控JAK-STAT信号通路在高血压血管重构中的作用  

The role of lymphocyte adaptor protein in regulating JAK-STAT signaling pathway in hypertensive vascular remodeling

作　　者：阿燕·西合斯 罗健[1] 邵明明 张玉玺 张源明[1] 王凌鹏[1] Ayan·Xihesi;LUO Jian;SHAO Mingming;ZHANG Yuxi;ZHANG Yuanming;WANG Lingpeng(Department of Heart Failure,First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China)

机构地区：[1]新疆医科大学第一附属医院心力衰竭科,乌鲁木齐830054

出　　处：《国际心血管病杂志》2021年第3期168-173,共6页International Journal of Cardiovascular Disease

基　　金：新疆维吾尔自治区科技支疆项目(2017E0268)。

摘　　要：目的:探讨淋巴细胞连接蛋白(LNK)调控Janus激酶(JAK)/信号转导与转录激活子(STAT)信号通路在高血压血管重构中的作用。方法:选取大鼠胸主动脉平滑肌细胞,构建高血压细胞模型。实验分组为对照组、血管紧张素(Ang)Ⅱ组、AngⅡ+空载组、AngⅡ+LNK组。流式细胞仪检测血管平滑肌细胞(VSMC)的细胞周期、凋亡及增殖水平;实时荧光定量聚合酶链反应检测各组LNK、JAK2、STAT3的mRNA表达水平;Western blot检测各组LNK、STAT3、磷酸化STAT3(p-STAT3)、JAK2、磷酸化JAK2(p-JAK2)的蛋白表达水平。结果:(1)各组细胞周期、凋亡及增殖水平比较:与对照组比较,Ang组和AngⅡ+空载组处于细胞休眠期(G0期)/DNA合成前期(G1期)的细胞减少,处于DNA合成期(S期)和DNA合成后期(G2期)/分裂期(M期)的细胞增加;与AngⅡ+空载组比较,AngⅡ+LNK组处于G0/G1期的细胞增加,处于S期、G2/M期的细胞减少。AngⅡ组和AngⅡ+LNK组细胞增殖水平高于对照组,凋亡率明显低于对照组;AngⅡ+LNK组细胞增殖水平低于AngⅡ组和AngⅡ+空载组,凋亡率明显高于AngⅡ组和AngⅡ+空载组(P均<0.05)。(2)各组mRNA表达水平比较:AngⅡ组和AngⅡ+空载组中STAT3、JAK2的mRNA表达水平明显高于对照组;AngⅡ+LNK组中STAT3、JAK2的mRNA表达水平明显低于AngⅡ组和AngⅡ+空载组(P均<0.05)。(3)各组蛋白表达水平比较:AngⅡ组和AngⅡ+空载组p-STAT3、p-JAK2的蛋白表达水平明显高于对照组;AngⅡ+LNK组p-STAT3、p-JAK2的蛋白表达水平明显低于AngⅡ组和AngⅡ+空载组(P均<0.05)。结论:LNK可能通过负性调节JAK/STAT信号通路参与高血压的血管重构。Objective:To investigate the role of lymphocyte adaptor protein(LNK)in regulating Janus kinase(JAK)/signal transduction and activators of transcription(STAT)signaling pathway in vascular remodeling in hypertension.Methods:Rat thoracic aortic smooth muscle cells were selected to construct a hypertensive cell model.The cells were divided into the control group,AngⅡgroup,AngⅡno-load group and AngⅡ+LNK group.Cell cycle,apoptosis and proliferation of vascular smooth muscle cells(VSMC)were detected by flow cytometry.The mRNA expression level of LNK,JAK2 and STAT3 was detected by real-time fluorescence quantitative PCR in each group.Western blot was used to detect protein expression levels of LNK,STAT3,phosphorylated STAT3(p-STAT3),JAK2,phosphorylated JAK2(p-JAK2)in each group.Results:(1)Comparison of cell cycle,apoptosis and proliferation levels in each group.Compared with the control group,the cells in cell dormancy stage(G0)/early stage of DNA synthesis(G1)decreased in AngⅡgroup and AngⅡno-load group,while the cells in DNA synthesis stage(S)and the DNA synthesis stage(G2)/division stage(M)increased.Compared with the AngⅡno-load group,the cells in G0/G1 stage increased in AngⅡ+LNK group,while the cells in S and G2/M period decreased.The proliferation levels in AngⅡand AngⅡ+no-load groups were higher than those in control group,and the apoptosis rates were significantly lower than that of the control group.VSMC cell proliferation level in AngⅡ+LNK group was lower than that in AngⅡgroup and AngⅡno-load group,and the apoptosis rate was significantly higher than that in AngⅡgroup and AngⅡno-load group(all P<0.05).(2)Comparison of mRNA expression levels among groups.The mRNA expression levels of STAT3,JAK2 in AngⅡgroup and AngⅡno-load group were significantly higher than those in control group.The mRNA expression levels of STAT3,JAK2 in AngⅡ+LNK group were significantly lower than those in AngⅡgroup and AngⅡno-load group(all P<0.05).(3)Comparison of protein expression levels in each gr

关 键 词：高血压 淋巴细胞连接蛋白 JANUS激酶 信号转导与转录激活子 血管重构 

分 类 号：R544.1[医药卫生—心血管疾病]