GPNMB调节凋亡对猴脑缺血模型的神经保护作用研究

Brain stroke has been one of the most common causes of death with a high morbidity and mortality. Glycoprotein nonmetastatic melanoma protein B (GPNMB) would be expressed in various tissues and cells. It plays an important role in regulating of inflammatory responses and apoptosis, and activating of survival signals. This project is to study the neuroprotective effects and mechanisms of GPNMB therapy in thrombotic middle cerebral artery occlusion model in Rhesus monkey. The stroke model will be made by autologous thromboembolic cerebral artery occlusion. MRI scanning and TTC staining will be performed for caculating stroke volume after 24 hours ischemia. Neurological defects scores test will be performed from 24 hours to 30 days after ischemia. Brain tissues will be stained for observing pathological change. The levels of Bcl-2, Bax and caspase3 expression will be measured after 24 hours ischemia. The project will study the neuroprotection and mechanism of GPNMB therapy on focal cerebral ischemia in rhesus monkey.

脑缺血性疾病的发病率和死亡率都较高，危害人类健康，目前临床有效的治疗药物少。非转移性黑色素瘤糖蛋白B（Glycoprotein nonmetastatic melanoma protein B，GPNMB）是一种可以在多种组织和细胞中表达的糖蛋白，与炎症反应、细胞免疫、细胞坏死和凋亡都有一定的关系。本项目采用恒河猴为研究对象，股动脉插管至大脑中动脉，采用自体血栓栓塞大脑中动脉分支构建脑缺血模型，GPNMB治疗后，MRI扫描监测脑缺血范围，缺血24小时后脑组织TTC染色测量脑梗死体积，同时检测凋亡基因Bcl-2、Bax和Caspase3的表达。栓塞后连续监测30天行为学表现，评价神经功能缺陷；栓塞后30天取脑组织HE染色观察组织和细胞学改变。本项目研究GPNMB治疗在猴脑缺血模型中的神经保护作用及治疗机制，进一步完善猴脑缺血模型的造模和监测方法，为GPNMB治疗脑缺血提供更多理论和实践基础。

脑缺血性疾病的发病率和死亡率都较高，危害人类健康，目前临床有效的治疗药物少。非转移性黑色素瘤糖蛋白B（Glycoprotein nonmetastatic melanoma protein B，GPNMB）是一种可以在多种组织和细胞中表达的糖蛋白，与炎症反应、细胞免疫、细胞坏死和凋亡都有一定的关系。本项目采用恒河猴为研究对象，股动脉插管至大脑中动脉，采用自体血栓栓塞大脑中动脉分支构建脑缺血模型，结果显示GPNMB治疗后，猴脑梗死体积明显减少，栓塞后连续监测30天行为学表现，神经功能缺陷改善。GPNMB治疗能凋亡基因Bcl-2表达上调，Bax和Caspase3的表达下调。GPNMB治疗能有效减少猴脑缺血模型脑梗死体积，其机制可能和调节凋亡基因的表达有关。