动脉内膜增生是糖尿病慢性血管病变的主要病理学基础，尚无有效治疗手段。高血糖诱导血管平滑肌细胞的异常增殖并迁移入内膜是主要发病机制。细胞外基质(ECM)的改变与血管内膜增生及再狭窄关系密切，但机制不明。我们前期研究发现:高血糖激活PARP-1调节基质金属蛋白酶(MMPs)的活性参与ECM的重构影响血管平滑肌细胞的迁移与增值。我们提出PARP-1可能通过调节MMPs的活性调控ECM的代谢参与糖尿病内膜增生的发生假说。通过mRNA差异表达的检测发现高血糖激活PARP-1可特异性抑制TFPI-2的表达。TFPI-2是一种肿瘤抑制因子，在ECM完整性，癌基因的调控及肿瘤细胞增殖等起着重要作用。本研究将研究PARP-1介导TFPI-2转录调控MMPs的活性与糖尿病内膜增生的分子机制，阐明糖尿病加速血管内膜增生的病理机制，为糖尿病引起的慢性血管病变治疗寻求新的治疗靶点。

Artery intimal hyperplasia is the main pathological basis of chronic vascular lesions in diabetes, there is no effective treatment high blood sugar induced abnormal vascular smooth muscle cell proliferation and migration into the lining is the main pathogenesis of extracellular matrix (ECM) change closely associated with intimal hyperplasia and restenosis, but the mechanism is unknown pilot study, we find that high blood sugar activates PARP-1 regulating the activity of matrix metalloproteinases (MMPs) involved in the reconstruction of the ECM affect the migration of vascular smooth muscle cells and value-addedWe proposed the hypothesis that parp-1 may regulate the metabolism of ECM by regulating the activity of MMPs and participate in the occurrence of diabetic endometrial hyperplasia. Through the detection of mRNA differential expression, it was found that the activation of PARP-1 by hyperglycemia can specifically inhibit the expression of TFPI-2, which is a tumor suppressor and plays an important role in the integrity of ECM, the regulation of oncogenes and the proliferation of tumor cells. This study will investigate the activity of PARP-1 mediated TFPI-2 transcriptional regulation of MMPs and the molecular mechanism of diabetic endometrial hyperplasia, clarify the pathological mechanism of accelerated diabetic endometrial hyperplasia, and seek new therapeutic targets for the treatment of diabetic chronic vascular diseases.