HMGB1通过TLR2-Myd88途径调控糖尿病中vWF水平

摘要

Objective To investgate the role of HMGB1-TLR2-Myd88 pathway in the transcriptional regulation of vWF in diabetes.Methods The diabetic module was established by using alloxan.The agonists and siRNA of TLR2 and the inhibitor of HMGB1 were used to detcted the role of HMGB1-TLR2-MyD88 pathway in the regulation of vWF.Results The vWF level was higher in the bone marcrophages in diabetic mice group (P ＜ 0.05).TLR2 agonists could upregulate the level of TLR2-Myd88 and vWF in the normal control group (P ＜ 0.05).TLR2 siRNA could downregulate the level of TLR2-Myd88 and vWF in the diabetic mice module(P ＜0.05).HMGB1 was higher in diabetic mice group.The HMGB1 inhibitor could decrease the expression of TLR2-Myd88 pathway and vWF level(P ＜ 0.05).Conclusion This study showed that HMGB1 released in diabetic mice act as an endogenous ligand of TLR2 and upregulate vWF through TLR2-MyD88 pathway.%目的 探究高迁移率族蛋白(l HMGB1)-TLR2-MyD88通路在调节糖尿病中血管性血友病因子(vWF)水平的作用.方法 使用四氧嘧啶建立糖尿病小鼠模型,使用TLR2抑制剂和激动剂以及HMGB1抑制剂观察糖尿病小鼠中HMGBl-TLR2-MyD88通路中蛋白水平的变化以及小鼠骨巨噬细胞和血浆中vWF含量.结果 糖尿病小鼠中骨巨噬细胞vWF含量比正常小鼠高(P＜0.05),使用TLR2激动剂后正常小鼠中TLR2、MyD88和vWF水平升高(P＜0.05),使用TLR2沉默RNA刺激糖尿病小鼠,可降调TLR2、MyD88和vWF水平(P＜0.05).糖尿病小鼠组中HMGB1水平高于正常小鼠组(P＜0.05),且使用HMGB1抑制剂后TLR2/MyD88通路以及vWF水平下调(P＜0.05).结论 本研究表明糖尿病小鼠中表达升高的HMGB1可作为TLR2的一种内源性配体激活TLR2-MyD88通路调节血浆中vWF水平.