硝普钠与尼莫地平治疗大鼠脑出血损伤的疗效及与凝血酶受体-1表达的相关研究

Efficacy of nitroprusside and nimodipine in treatment of cerebral hemorrhage in rats and its correlation with thrombin receptor-1 expression

摘要:

的探讨硝普钠与尼莫地平治疗大鼠脑出血（ICH），降低大鼠脑血肿及脑出血后神经元损伤的疗效及与凝血酶受体-1（PAR1）表达的相关性。方法用30 只雄性Wista 大鼠（200～220 g）复制脑出血ICH 模型，并随机分为3 组（每组10 只），分别是假手术组、脑出血组和联合治疗组。大鼠于ICH手术成功后48 h处死，收集大鼠脑组织备用。采用TUNEL法检测细胞凋亡的发生；干燥法检测大鼠脑组织水含量；采用免疫组织化学法和蛋白质印迹法Western blot检测PAR1 蛋白的表达。结果与假手术组比较，脑出血组和联合治疗组中凋亡细胞数和脑组织水含量增多（均p=0.000），而联合治疗组中凋亡细胞数和脑组织水含量低于脑出血组（均p=0.000）；与假手术组PAR1 蛋白含量（0.673±0.121）比较，脑出血组PAR1 蛋白含量（2.187±0.233）和联合治疗组PAR1 蛋白含量（1.434±0.168）上升，差异有统计学意义（p =0.000），与脑出血组比较，联合治疗组PAR1 蛋白含量下降，差异有统计学意义（p =0.000）；Western blot结果与免疫组织化学结果一致。结论硝普钠与尼莫地平通过对PAR1 的调控治疗大鼠脑出血损伤，具有神经保护作用。

Abstract:

To investgate the effect of sodium nitroprusside and nimodipine on cerebral hemorrhage (ICH) in rats and its correlation with expression of thrombin receptor-1 (PAR1). Methods Thirty male Wistar rats (200-220 g) were randomly divided into 3 groups (n = 10 each): sham operation group, cerebral hemorrhage group and combination therapy group. Rats were sacrificed 48 hours after successful ICH operation. The apoptosis of neurons was detected by TUNEL method. The water content of brain tissue was detected. The expression of thrombin receptor-1 (PAR1) protein was detected by Immunohistochemistry and Western blot. Results Compared with the sham group, the number of apoptotic cells and water content in cerebral hemor-rhage group and combination therapy group were significantly increased (p = 0.000), while the number of apoptotic cells and water content of brain tissue in combination group were significantly lower than the cerebral hemorrhage group (p = 0.000). Compared with sham group, PAR1 protein expression in cerebral hemorrhage group (2.187 ±0.233) and PAR1 protein expression in ICH group (1.434 ±0.168) were significantly increased (0.673 ±0.121) (p = 0.000). Compared with ICH group, the PAR1 protein expression in the combination group significantly decreased (p = 0.000), and the difference was statistically significant ( p= 0.000). The results ofwestern blot were consistent with immunohistochemical results. Conclusions Sodium nitroprusside and nimodip-ine have neuroprotective effects on cerebral hemorrhage by regulating the expression of thrombin receptor-1 (PAR1) in rats.