脑卒中是我国的常见病，致死率高，但治疗手段非常有限。因此，新药物开发十分必要。我们前期工作表明：缺血性脑卒中后，死亡相关蛋白激酶1（DAPK1）活性增强，与p53蛋白相互作用，介导神经细胞死亡。特异性多肽TAT-p53DM可阻断二者的相互作用，降低神经细胞死亡水平，促进神经功能恢复。但长期使用多肽是否引起神经胶质瘤的发生尚不清楚。我们近期预实验结果表明：OGD处理的神经元长期使用治疗性多肽TAT-p53DM后异常增生；在人脑胶质瘤中，DAPK1表达下降并发生核转位；DAPK1与importin 5之间存在相互作用。在此基础上，本研究拟在离体与在体缺血模型，持续给予特异性多肽治疗后，通过观察DAPK1和importin 5与胶质瘤发生的关系，并在人的胶质瘤中进一步验证，深入研究特异性多肽引起胶质瘤发生的细胞分子机制，为客观评估TAT-p53DM治疗缺血性卒中的安全性与疗效提供依据。

Stroke is a common disease in our country, which has high fatality rate and limited treatment.Therefore, it is necessary to develop new drugs. Our previous work showed that: after ischemic stroke, the activity of death associated protein kinase 1 (DAPK1) increased, and DAPK1 mediated neuronal cell death by interaction with protein p53. The specific poly-peptide TAT-p53DM can block the interaction of DAPK1 and p53, reducing neuronal death and promoting the recovery of neurological disfunction. But whether the long-term use of poly-peptide can induce glioma is not clear. Our recent results show that: OGD treated neurons proliferated abnormally after a long-term use of therapeutic poly-peptide TAT-p53DM; In human gliomas, the expression of DAPK1 decreased and DAPK1 translocated into nuclear; DAPK1 and importin 5 interacted with each other strongly. On the basis of these studies, our study suppose to study the mechanism of tumorigenesis of gliomas in in vitro and in vivo ischemia models treated with long-term polypeptide TAT-p53DM by observating DAPK1 and importin 5 interaction, and then validate the mechanism in human glioma, provide the evidence to evaluate the safty and efficacy of TAT-p53DM in the treatment of ischemic stroke.