| 摘要: |
| 目的 探讨Janus蛋白酪氨酸激酶2/信号转导子和转录激活子3(JAK2/STAT3)信号通路在2型糖尿病大血管病变发病机制中的作用。方法 取健康志愿者、单纯2型糖尿病患者和2型糖尿病大血管病变患者的血清孵育人脐静脉内皮细胞(HUVEC)24 h,通过给予JAK2特异性抑制剂AG490阻断JAK2/STAT3信号通路,并将细胞按不同处理方式分为对照组(NC组)、单纯糖尿病组(DM组)、糖尿病大血管病变组(DV组)、单纯糖尿病+AG490组(DM+AG490组)及糖尿病大血管病变+AG490组(DV+AG490组),各30例。采用实时定量PCR技术检测各组细胞JAK2、STAT3、血管内皮生长因子(VEGF)和血管内皮生长因子受体(FLT1)mRNA表达水平,蛋白质印迹法检测JAK2、STAT3和磷酸化STAT3(p-STAT3)蛋白表达量。结果 与NC组比较,DM组和DV组HUVEC细胞内JAK2、STAT3mRNA和JAK2、p-STAT3的蛋白表达水平均上调(P<0.05),且DV组JAK2、STAT3 mRNA和JAK2、p-STAT3蛋白表达水平均高于DM组(P<0.05)。DM+AG490组和DV+AG490组的JAK2、STAT3 mRNA和JAK2、p-STAT3蛋白表达水平分别低于DM组、DV组(P<0.05)。与NC组和DM组比较,DV组VEGF和FLT1 mRNA的表达水平上调(P<0.05);而与DV组比较,DV+AG490组VEGF和FLT1 mRNA的表达水平均下调(P<0.05)。结论 JAK2/STAT3信号通路可能参与2型糖尿病大血管病变的发病过程。 |
| 关键词: 2型糖尿病 糖尿病血管病变 动脉粥样硬化 JAK2/STAT3信号通路 酪氨酸磷酸化抑制剂 |
| DOI：10.16781/j.0258-879x.2016.04.0452 |
| 投稿时间：2015-11-23修订日期：2016-01-03 |
| 基金项目:国家自然科学基金(81560147);贵州省科技攻关项目[黔科合SY字(2012)3116号];贵州省科学技术基金项目[黔科合J字LKZ(2013)53号,黔科合J字LKZ(2012)28号];遵义医学院博士启动基金(F-588). |
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| Expression of JAK2/STAT3 signaling pathway in human umbilical vein endothelial cells exposed to the serum of type 2 diabetic macroangiopathy patients |
| LI Feng-ping,YANG Meng-xue*,LI Xian-wen,YANG Bo,LI Si-cheng,LI Jian,AN Xiao-juan |
(Department of Endocrinology, Affiliated Hospital of Zunyi Medical College, Zunyi 563003, Guizhou, China
*Corresponding author) |
| Abstract: |
| Objective To investigate the role of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signaling pathway in the pathogenesis of type 2 diabetic macroangiopathy. Methods The human umbilical vein endothelial cells (HUVECs) were incubated for 24 h with the serum of healthy volunteers, simple type 2 diabetic patients and patients with type 2 diabetic macroangiopathy. JAK2 specific inhibitor AG490 was used to block the JAK2/STAT3 signaling pathway. According to different treatments, the cells were divided into normal control group (NC group, n=30), simple diabetes mellitus group (DM group, n=30), type 2 diabetic macroangiopathy group (DV group, n=30), DM+AG490 group (DM+AG490 group, n=30) and DV+AG490 group (DV+AG490 group, n=30). Real-time quantitative PCR technique was used to detect the mRNA expression of JAK2, STAT3, vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (FLT1) in each group. Western blotting analysis was used to detect the protein expression of JAK2, STAT3 and phosphorylated STAT3(p-STAT3). Results Compared with the NC group, the expression of JAK2, STAT3 mRNA and JAK2, and p-STAT3 protein were significantly up-regulated in DM and DV groups (P<0.05), and the expression of JAK2, STAT3 mRNA and JAK2, p-STAT3 protein in DV groups were significantly higher than those in DM group (P< 0.05). The expression of JAK2, STAT3 mRNA and JAK2, p-STAT3 protein in DM+AG490 group and DV+AG490 group were significantly lower than those in the DM group and DV group (P< 0.05). Compared with the NC and DM group, the expression of VEGF, FLT1 mRNA was significantly up-regulated in DV group(P<0.05). Compared with the DV group, the expression of VEGF and FLT1mRNA were significantly reduced in DV+AG490 group (P< 0.05). Conclusion JAK2/STAT3 signaling pathway may play a role in the pathogenesis of type 2 diabetic macroangiopathy. |
| Key words: type 2 diabetes mellitus diabetic angiopathies artherosclerosis JAK2/STAT3 signaling pathway tyrphostins |
