二肽基肽酶4抑制剂对缺血性卒中以及糖尿病合并缺血性卒中的治疗作用及免疫机制研究

免疫炎症反应在缺血性卒中及糖尿病的发生发展中均发挥关键作用，但是糖尿病合并缺血性卒中的相关研究缺乏。我们的前期研究发现，免疫调节治疗在缺血性卒中的动物模型中有效，且糖尿病合并缺血性卒中后机体的免疫炎症反应更复杂。二肽基肽酶4（DPP-4）抑制剂不仅是一种广泛应用的降糖药，还被发现在很多疾病中发挥免疫调节作用。因此我们提出DPP-4抑制剂可能通过免疫调控作用来改善缺血性卒中，特别是糖尿病合并缺血性卒中的病情。本课题以星形胶质细胞和2型糖尿病合并缺血性卒中的动物模型（MCAO）为研究对象，通过免疫学、分子、细胞生物学及病理学等手段阐明糖尿病小鼠发生缺血性卒中后的动态炎症过程；探讨DPP-4抑制剂对缺血性卒中以及糖尿病合并缺血性卒中模型的治疗作用以及其中的免疫调控机制。上述问题的解决不仅丰富合并糖尿病的缺血性卒中小鼠的病理生理的内容，并且对临床上有糖尿病基础的缺血性卒中患者的治疗提供了新的思路。

Both the domestic and foreign researches indicated that immunologic mechanism play an important role in the pathogenesis of ischemic stroke and diabetes mellitus, but the immunologic study on diabetes complicated with ischemic stroke is still lacking. Our preliminary work have demonstrated immunoregulation effective in Middle Cerebral Artery Occlusion (MCAO) rats, and the inflammatory immune resonse is more complicated when the ischemic stroke based on diabetes. Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new type of antidiabetic drugs, which have showed immunomodulatory effects in other diseases. So we hypothesise that DPP-4 inhibitors could improve the prognosis of MCAO and diabetic MCAO mice by immunomodulatory mechanism. The objects of our project are astrocytes and diabetic MCAO mice. The techniques of immunology, molecular, cell biology and pathology would be used in the project. The aims of our project are to clarify the dynamic inflammatory response of mice after diabetic ischemic stroke and study the effect of DPP-4 inhibitors on MCAO and diabetic MCAO mice, including the immunologic mechanisms involved. Our project not only has important impact on clarifying the pathogenesis of cerebral ischemic stroke with diabetes, but aslo provides a new idea for the therapies of ischemic stroke patients with diabetes.