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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)24h,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、STAT3mRNA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FLT1mRNA的表达水平上调(P<0.05);而与DV组比较,DV+AG490组VEGF和FLT1mRNA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。
Objective To investigate the role of Janus protein tyrosine kinase 2 / signal transducer and activator of transcription 3 (JAK2 / STAT3) signaling pathway in the pathogenesis of type 2 diabetic macroangiopathy. Methods Human umbilical vein endothelial cells (HUVECs) were incubated with serum from healthy volunteers, patients with type 2 diabetes mellitus and type 2 diabetic patients with macrovascular disease for 24 hours. The JAK2 / STAT3 signal pathway was blocked by JAK2 specific inhibitor AG490, The cells were divided into control group (NC group), diabetic group (DM group), diabetic macroangiopathy group (DV group), DM + AG490 group (DM + AG490 group) and diabetic macroangiopathy Group (DV + AG490 group), each 30 cases. The expression of JAK2, STAT3, vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (FLT1) mRNA in each group were detected by real-time quantitative PCR. JAK2, STAT3 and p-STAT3 were detected by Western blotting. Protein expression level. Results Compared with NC group, the protein expression of JAK2, STAT3 and JAK2 and p-STAT3 in DM and DV groups were up-regulated (P <0.05), and the expression of JAK2, STAT3 and JAK2, p-STAT3 The levels were higher than DM group (P <0.05). The expression of JAK2, STAT3mRNA and JAK2, p-STAT3 protein in DM + AG490 group and DV + AG490 group were lower than those in DM group and DV group respectively (P <0.05). Compared with NC group and DM group, the expression of VEGF and FLT1mRNA in DV group were up-regulated (P <0.05). Compared with DV group, the expression of VEGF and FLT1mRNA in DV + AG490 group were down-regulated (P <0.05). Conclusion JAK2 / STAT3 signaling pathway may be involved in the pathogenesis of type 2 diabetic macroangiopathy.