氧化还原HMGB1介导间充质干细胞血管修复对动脉粥样硬化的影响

摘要：目的 观察氧化还原状态高迁移率族1蛋白（High mobility group box 1 protein, HMGB1）对间充质干细胞（mesenchymal stem cell, MSC）增殖、迁移及向血管细胞（内皮细胞及平滑肌细胞）分化的影响，初步探讨氧化还原状态HMGB1介导MSC血管修复对动脉粥样硬化的影响。方法 二硫苏糖醇(dithiothreitol, DTT)及过氧化氢（H2O2）处理 HMGB1，使其处于不同氧化还原状态，使用上述氧化还原状态HMGB1处理体外培养MSC，不做处理为空白组。CCK-8检测细胞增殖力；Transwell 试验检测细胞迁移力；免疫荧光实验及流式细胞仪技术检测细胞分化情况。结果 DTT还原的HMGB1促进MSC增殖，增强其对MSC迁移及向血管内皮细胞分化的促进作用，并且增强其对MSC向血管平滑肌细胞分化的抑制作用； H2O2氧化的HMGB1使其对MSC增殖、迁移及向血管细胞（内皮细胞及平滑肌细胞）分化的影响减弱甚至消失。结论 还原状态HMGB1能够通过促进MSC增殖，增强其对MSC迁移及向血管内皮细胞分化的促进作用，并且增强其对MSC向血管平滑肌细胞分化的抑制作用，进而抑制动脉粥样硬化；氧化状态HMGB1通过使其对MSC增殖、迁移及向上述血管细胞分化的影响减弱甚至消失，进而促进动脉粥样硬化。

Effect of redox HMGB1 mediated MSC vascular repair on atherosclerosis

Abstract: Objective To observe the effects of redox state High mobility group box 1 protein (HMGB1) on the proliferation, migration and differentiation of MSCs into vascular cells (vascular endothelial cells and vascular smooth muscle cells), and to preliminary explore the redox state HMGB1 Mediate the effect of MSC vascular repair on atherosclerosis. Methods HMGB1 was treated with DTT and H2O2 to make them in different redox states. MSCs cultured in vitro were treated with the above redox state HMGB1, and the blank group was not treated. CCK-8 was used to detect cell proliferation; Transwell test was used to detect cell migration; immunofluorescence experiments and flow cytometry were used to detect cell differentiation. Results HMGB1 reduced by DTT promoted the proliferation of MSCs, enhanced its promotion of MSC migration and differentiation into vascular endothelial cells, and enhanced its inhibitory effect on the differentiation of MSCs into vascular smooth muscle cells; HMGB1 oxidized by H2O2 caused its proliferation, migration and The effect of differentiation into vascular cells (vascular endothelial cells and vascular smooth muscle cells) weakens or even disappears. Conclusion The reduced state HMGB1 can promote the proliferation of MSC, enhance its promotion of MSC migration and differentiation into vascular endothelial cells, and enhance its inhibitory effect on the differentiation of MSC into vascular smooth muscle cells, thereby inhibiting atherosclerosis. The effect on MSC proliferation, migration and differentiation into the above-mentioned vascular cells is weakened or even disappeared, thereby promoting atherosclerosis.