【摘要】 目的研究内皮瞬时受体电位香草酸亚型4(TRPV4)对大鼠脑缺血/再灌损伤的保护作用及其机制。方法将30只SD大鼠随机分成sham组和大脑中动脉闭塞(MCAO)组和4α-PDD干预组。MCAO 3 h,再灌注72 h。采用TTC方法检测脑梗死体积、Garcia评分评估神经损伤程度和定量RT-PCR检测内皮型一氧化氮合酶(e NOS)、血管内皮生长因子A受体-2(VEGFA-2)和血管内皮生长因子A(VEGFA) mRNA表达;免疫组化检测CD3和Sox2蛋白表达。结果与sham组相比,MCAO组大鼠脑梗死体积及神经功能缺损明显增加(P<0. 001)。4α-PDD可使MCAO后大鼠脑梗死体积显著缩小(P<0. 001),并改善神经功能缺损(P<0. 05)。4α-PDD显著增加缺血半影区e NOS、VEGFA和VEGFA-2 mRNA表达(P<0. 001)并使缺血半影区内微血管密度显著增加(P<0. 001),而且神经祖细胞(NPC)在缺血半影区增殖和迁移均增加。结论 4α-PDD可能通过促进大鼠缺血半影区血管和神经再生改善MCAO后神经功能损伤。更多还原

【Abstract】 Objective To test whether the endothelial transient receptor potential cation channel subfamily V member 4( TRPV4) activation may improve functional recovery in rats subjected to brain ischemia/reperfusion and its mechanisms. Methods Thirty SD rats were randomly divided into sham group,middle cerebral artery occlusion( MCAO) group and 4α-PDD group. The volume of cerebral infarction was detected by TTC method; the degree of nerve injury was evaluated by Garcia score; the expression of endothelial nitric oxide synthase( eNOS),VEGF receptor-2( VEGFA-2) and vascular endothelial growth factor A( VEGFA) mRNA were detected by quantitative RTPCR; CD3 and Sox2 proteins were detected by immunohistochemistry. Results Compared with sham group,the volume of cerebral infarction and neurological deficit in MCAO group increased significantly( P<0. 001). 4α-PDD reduced infarct volume( P<0. 001) and improved functional outcomes( P<0. 05) on day 3 after MCAO.TRPV4 activation significantly increased endothelial nitric oxide synthase( e NOS) expression in the ischemic region( P<0. 001). The expressions of vascular endothelial growth factor A( VEGFA) and VEGF receptor-2 were signifi-cantly higher in the 4α-PDD group( P<0. 001). 4α-PDD treatment also caused a significantly increase of microvessel density( P < 0. 001). In addition,Neural progenitor cells( NPC) proliferation and migration in the ischemic hemisphere were increased,respectively. Conclusions TRPV4 activation by 4α-PDD may improve functional recovery through angiogenesis and neurogenesis after MCAO.更多还原