骨髓基质干细胞加重糖尿病脑缺血损伤的新机制-RAGE介导的信号通路

糖尿病患者缺血性脑血管病的发病率、致残率和死亡率均远高于正常人群，亟需探寻有效防治措施。我们的前期研究发现骨髓基质干细胞在治疗糖尿病脑缺血再灌注损伤时，与其在治疗非糖尿病缺血性脑血管病的情形相反，不仅不能改善神经功能的恢复，反而会加重血管损伤，造成以上结果的具体机制目前尚不清楚。.由于晚期糖基化终产物受体介导的炎症反应在脑损伤局部的激活是糖尿病脑缺血再灌注损伤后预后差的重要原因，我们假设：骨髓基质干细胞加重糖尿病脑缺血再灌注损伤的原因可能与进一步激活晚期糖基化终产物受体介导的炎症反应有关。本实验拟以晚期糖基化终产物受体介导的炎症反应通路为切入点，从整体、细胞和分子水平阐明骨髓基质干细胞加重糖尿病脑缺血再灌注损伤的分子机制，为骨髓基质干细胞在临床，特别是在糖尿病脑血管病中有效安全应用提供新思路。

Diabetic patients have a higher risk of ischemic stroke and poorer outcomes after ischemic stroke. Therefore, development of effective therapies for ischemic stroke in diabetic patients is crucial. Transplantation of bone marrow stromal cells (BMSCs) can improve functional recovery after ischemic stroke in rats without diabetes. However, our previous data have indicated that BMSCs treatment initiated 24 after ischemic stroke in diabetic rats increases vascular damage and fails to improve functional outcomes, the mechanisms by which bone marrow stromal cells based treatment increases vascular damage and fails to improve functional outcomes remains unclear. .The poorer outcomes after ischemic stroke in diabetic rats has been attributed to activation of the receptor for advanced glycation endproducts (RAGE) mediated signal pathway in the ischemic penumbra. Based on the above data, we made the assumption that the adverse effects of BMSCs treatment of stroke in diabetic rats may be attributed to further activation of a RAGE-dependent signal pathway. So we chose to focus on this pathway for our investigation, and we intend to clarify the possible mechanisms by which BMSCs treatment increases vascular damage and fails to improve the outcomes after ischemic stroke in diabetic rats. This study may offer new ideas for using BMSCs to effectively treat diabetes who have suffered from a stroke.