蛋白酶激活受体-1在凝血酶诱导大鼠脑损伤及神经再生中的作用

Roles of protease-activated receptor-1 in thrombin-induced brain injury and neurogenesis in rats

目的:研究蛋白酶激活受体的激活在凝血酶所致大鼠脑损伤中的作用,以及与神经细胞再生的关系。方法:90只成年雄性SD大鼠随机分为5组,分别海马注射生理盐水(NS)、凝血酶以及3种蛋白酶激活受体的特异性激动剂,注射1 d、3 d、7 d后,用HE染色检测海马面积变化,用胶质纤维酸性蛋白(GFAP)染色检测星形胶质细胞数量和形态,用Flouro-Jade C染色检测神经元变性,微管相关蛋白(DCX)标记检测神经细胞再生。结果:与NS组比较,注射凝血酶和蛋白酶激活受体-1激动剂后1～3 d出现海马面积显著增大(P<0.05),7 d出现海马面积明显缩小;注射后1～7 d GFAP阳性细胞、Flouro-Jade C阳性细胞增多(P<0.05);注射后3～7 d DCX阳性细胞增多(P<0.05)。而注射蛋白酶激活受体-3激动剂和蛋白酶激活受体-4激动剂均未见上述变化。结论:蛋白酶激活受体-1激活可能参与凝血酶所致的急性期脑损伤以及后期的神经再生。

Objective： To investigate the roles of protease-activated receptors（PARs） in thrombin-induced brain injury and neurogenesis in rats.Methods： Ninety male SD rats were randomly assigned to receive intra-hippocampus injection of NS,thrombin or specific agonists of 3 protease-activated receptors（PAR-1,PAR-3 and PAR-4）,respectively.At 1,3 and 7 d after injection,the area of the hippocampus was determined with HE staining,the density and morphology of astrocyte were detected with GFAP staining,degenerated neurons were detected with Flouro-Jade C staining,and the neurogenesis was examined with DCX staining.Results： Compared to NS injection,the area of the hippocampus significantly increased at 1-3 d and decreased at 7 d after the injection of thrombin and PAR-1 agonist（P0.05）.In addition,injection of thrombin and PAR-1 agonist significantly increased the density of astrocyte and Flouro-Jade C positive cells at 1-7 d after injection（P0.05）,and significantly increased the density of DCX positive cells at 3-7 d after injection（P0.05）.The injection of PAR-3 agonist and PAR-4 agonist had no affect on the area of the hippocampus,the density of astrocyte,Flouro-Jade C positive cells and DCX positive cells.Conclusion： The activation of protease-activated receptor-1 may be related to the thrombin-induced brain injury and neurogenesis in rat hippocampus.