老年小鼠脑缺血损伤加重的内皮祖细胞机制

Aging is one of the primary risk factors for ischemic stroke. Clinical studies have confirmed that elderly individuals not only have increased incidence of stroke, but also display worsened outcomes than younger patients. The severity of cerebral ischemic injury is related to impairing angiogenesis, which is closely related to the dysfunction of endothelial progenitor cells (EPC). Accordingly, we hypothesize that EPC dysfunction induced by aging aggravate cerebral ischemic injury. To test this hypothesis, this project will perform following 3 aims: 1) to determine the relationship between the aggravated cerebral ischemic injury produced by aging and EPC dysfunction; 2) to investigate the mechanisms underlying the EPC dysfunction in aging mice; 3) to investigate the effects of suppressing TSPs expression by RNA interference or Sodium Dichloroacetate (DCA) on EPC functions in aging mice. Therefore, this project may provide a new therapeutic strategy for aging-related cardio-cerebrovascular diseases.

衰老是脑卒中的主要危险因素之一。临床研究证实，与年轻患者相比，老年患者脑卒中普遍更加严重。研究表明，脑缺血损伤的严重程度与血管新生有关，而血管新生与内皮祖细胞(EPC)的功能密切相关。因此，我们推测老年小鼠的脑缺血损伤加重可能与其EPC功能受损有关。本项目拟通过下列实验来验证该假设：确定老年小鼠脑缺血损伤加重与EPC功能受损的关系；阐明老年小鼠EPC功能受损的机制；研究siRNA干扰凝血酶敏感蛋白（TSPs）表达对老年小鼠EPC功能的影响；研究二氯乙酸钠干预TSPs表达对老年小鼠EPC功能的影响。所以，本项目的研究有可能为衰老相关的心脑血管疾病的防治提供新的思路和参考。

众所周知，寻求有效的手段防治衰老相关心脑血管疾病（脑卒中等）具有极其重要的临床意义。我们的实验结果证实，老年小鼠的脑缺血损伤加重与其EPC功能受损有关。脑缺血损伤严重的老年小鼠血管新生数量也减少，而且血管新生数量的减少与内皮祖细胞(EPC)功能受损密切相关。实验结果还表明，老年小鼠EPC功能受损与该细胞中凝血酶敏感蛋白-1(TSP-1)和凝血酶敏感蛋白-2(TSP-2)基因表达水平升高有关。siRNA干扰和二氯乙酸钠（DCA）干预TSPs表达能够改善老年小鼠EPC的功能，进而减轻老年小鼠的脑缺血损伤。DCA与siRNA干扰具有类似的治疗效果，可能具有更大的临床应用潜力。因此，本研究为衰老相关心脑血管疾病的防治提供了新的思路和参考。