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TIMP-3基因靶向抑制p38信号通路对人腹主动脉瘤平滑肌细胞生物学特性的影响
作者：任明明1  王涛1  李敬来1  达青恩1  黄磊1  陈丕绩2  韩振1 
单位：1. 北京大学深圳医院 心血管外科, 广东 深圳 518036;
2. 深圳市第七人民医院 检验科, 广东 深圳 518081
关键词：组织金属蛋白酶抑制因子-3 p38信号通路 腹主动脉瘤 平滑肌细胞 生物学特性 
分类号：R732.2
出版年·卷·期（页码）：2019·38·第四期（687-693）
摘要：

目的：探讨组织金属蛋白酶抑制因子-3（tissue inhibitor of metalloproteinase-3，TIMP-3）靶向抑制p38信号通路对腹主动脉瘤（abdominal aortic aneurysms，AAAs）人血管平滑肌细胞（human vascular smooth muscle cells，HVSMCs）生物学特性的影响。方法：将HVSMCs分为Control组（不进行任何处理）、NC组（转染空载体）、TIMP-3组（转染TIMP-3载体）、SB203580组（加p38信号通路抑制剂SB203580）4组。采用qRT-PCR和Western blotting检测各组转染细胞中TIMP-3、p38MAPK、Bcl-2、Bax、Caspase-3的mRNA及蛋白表达水平；MTT法检测HVSMCs增殖能力；流式细胞术检测HVSMCs细胞周期和凋亡情况。结果：与Control组相比，TIMP-3组细胞中TIMP-3、Bcl-2的mRNA和蛋白表达量显著增加，p38MAPK、Bax、Caspase-3的mRNA和蛋白表达量显著下降（均P<0.05）；Control组与SB203580组相比，细胞中TIMP-3的mRNA和蛋白表达量差异无统计学意义（均P>0.05），而Bcl-2的mRNA和蛋白表达量显著增加，p38MAPK、Bax、Caspase-3的mRNA和蛋白表达量显著下降（均P<0.05）。相对于Control组，TIMP-3组和SB203580组细胞增殖能力显著提高，凋亡减少，G1期细胞比例减少，同时S期、G2期细胞比例显著增加（均P<0.05）。结论：TIMP-3基因可抑制p38信号通路的激活，进而促进HVSMCs增殖，抑制其凋亡，在腹主动脉瘤的发病中具有保护作用。

Objective: To investigate the effects of tissue inhibitor of metalloproteinase-3 (TIMP-3) gene on the biological characteristics of human vascular smooth muscle cells (HVSMCs) of abdominal aortic aneurysms (AAAs) through targeting p38 signaling pathway. Methods: HVSMCs were divided into four groups: control group (without any treatment), NC group (transfected with empty vector), TIMP-3 group (transfected with TIMP-3 vector), SB203580 group (transfected with p38 signaling pathway inhibitor SB203580). The mRNA and protein expression levels of TIMP-3, p38MAPK, Bcl-2, Bax and Caspase-3 were detected by qRT-PCR and Western blotting, the proliferation of HVSMCs was analyzed by MTT, and the cell cycle and apoptosis of HVSMCs were tested by flow cytometry. Results: Compared with the control group, the expression of TIMP-3 and Bcl-2 mRNA and protein in TIMP-3 group were increased significantly, while the expression of p38MAPK, Bax and Caspase-3 mRNA and protein were decreased (all P<0.05); compared with the control group, there was no significant difference in the expression of TIMP-3 mRNA and protein in SB203580 group (all P>0.05), but the expression of Bcl-2 mRNA and protein were increased in SB203580 group, and the expression of p38 MAPK, Bax and Caspase-3 were significantly decreased (all P<0.05).Compared with the control group, TIMP-3 group and SB203580 group showed a significant increase in cell proliferation, a significant decrease in apoptosis rate, a significant decrease in G1 phase, and a significant increase in S phase and G2 cell proportion (all P<0.05). Conclusion: TIMP-3 gene can inhibit the activation of p38 signaling pathway, promote the proliferation and inhibit the apoptosis of HVSMCs, and play a protective role in the pathogenesis of abdominal aortic aneurysm.
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