HSP47在高血压脑出血中的保护作用及其机制研究

高血压脑出血造成重大健康负担，但是高血压情况下血管的破裂机制尚不清楚。我们前期研究发现热休克蛋白47（heat shock protein 47，HSP47）的表达水平随着小鼠高血压脑出血的进展逐渐降低，随后检测高血压脑出血患者和正常对照组血浆中HSP47的含量，发现高血压脑出血患者血浆中的HSP47低于正常对照组。通过外源给予HSP47后，小鼠高血压脑出血的发生率及严重程度降低，由此推测HSP47对高血压脑出血可能有保护作用。本课题拟构建AAV9-HSP47敲低小鼠及HSP47条件性敲除小鼠，构建高血压脑出血模型，在整体生存率、MRI、病理水平验证这一假说。结合人脑血管内皮细胞的转录组测序结果及质谱分析结果找到HSP47参与的关键分子通路和直接作用蛋白，进一步阐明HSP47发挥保护作用的详细分子机制，这对高血压情况下血管的破裂机制有着重要意义，为高血压脑出血的基础研究及治疗提供新思路。

Hypertensive intracerebral hemorrhage is a serious clinical problem, which brings great burden to patients, but the mechanism of vessel rupture under the condition of cerebral blood pressure is still unclear. Our previous study found that the expression level of heat shock protein 47 (HSP47) decreased gradually with the progress of hypertensive intracerebral hemorrhage in mice.Then, HSP47 levels in plasma of hypertensive intracerebral hemorrhage patients and normal patients were detected, and HSP47 levels in plasma of hypertensive intracerebral hemorrhage patients were lower than that of normal patients. The incidence and severity of hypertensive intracerebral hemorrhage in mice decreased after exogenous administration of HSP47, suggesting that HSP47 may have a protective effect on hypertensive intracerebral hemorrhage. This project intends to build AAV9- HSP47 knock-down mice and HSP47 conditional knockout mice, and create a model of hypertensive cerebral hemorrhage on these mice, then the overall survival rate, MRI and pathological level will be analyzed to verify this hypothesis. Combined with the transcriptome sequencing results of human vascular endothelial cells and the results of spectrometry analysis, we will find the key molecular pathway and direct-acting proteins of HSP47, further clarifying the detailed molecular mechanism of HSP47 in ICH. This project has important significance for the mechanism of vessel rupture under hypertension and provides new ideas for basic research and treatment of hypertensive cerebral hemorrhage.