硫化氢对大鼠局灶性脑缺血/再灌注损伤的保护作用及其机制

摘要

目的：探讨硫化氢( H2 S)对大鼠局灶性脑缺血/再灌注损伤的保护作用及其机制。方法裔SD大鼠随机分成3组：假手术组、脑缺血/再灌注( I/R)组和硫氢化钠( NaHS)+ I/R。线栓法建立大鼠左侧大脑中动脉栓塞( MCAO)模型,缺血2 h,再灌注24 h后,计算各组死亡率、Longa评分标准进行神经功能缺陷评分,2,3,5-三苯基氯化四氮唑( TTC)染色测量脑梗死体积,免疫荧光法检测大脑皮质和海马组织中P2X7受体蛋白表达。结果 NaHS + I/R组大鼠死亡率(27.27%)明显低于I/R组(42.86%),该组大鼠神经功能缺陷评分也明显低于 I/R 组(P <0.05),且脑梗死体积(21.88%依3.53%)明显低于I/R组(36.71%依3.73%)( P<0.01)。免疫荧光结果显示,与假手术组相比,I/R组大脑皮质、海马 CA1区 P2X7阳性表达细胞数明显增多( P <0.01)；与I/R组相比,NaHS + I/R组大脑皮质、海马 CA1区P2X7阳性表达细胞数明显减少(P<0.01)。结论 H2S可对局灶性脑缺血/再灌注损伤大鼠发挥脑保护作用,其机制可能与下调P2X7受体蛋白表达有关。%Aim To investigate the protective effects of hydrogen sulfide ( H2 S) on focal cerebral ischemia/reperfusion injury in rats and the possible mechanisms. Methods Male Sprague Dawley rats were divided into three groups randomly: sham-operated group, cerebral ischemia/ reperfusion ( I/R) group and sodium hydro-sulfide ( NaHS ) + I/R group. The left temporary middle cerebral artery occlusion ( MCAO ) model was established by the line-embolism method. After rats were suffered 2h/24h ischemia/reperfusion stress, the mortality rate was evaluated, and the nervous function-al defect degree was evaluated by Longe scoring, the volumes of cerebral infarction was evaluated by 2 ,3 ,5-triphenyltetrazolium chloride ( TTC) staining, and the expression of P2X7 receptor protein in brain tissue was detected by the immunofluorescence method. Results The mortality rate in NaHS + I/R rats ( 29.41%) was obviously lower than those of I/R group ( 42 . 86%) . The nervous defect scores in NaHS + I/R rats were significant lower than those of I/R group ( P <0.05 ) . The volumes of cerebral infarction in NaHS +I/R group (21.88% ±3.53%) were significant lower than those of I/R group ( 36.71% ±3.73%) ( P <0.01 ) . The results of immunofluorescence showed that the positive expression cells of P2X7 receptor protein in cerebral cortex and hippocampal CA1 area of I/R group were significantly higher than those of sham-op-erated group(P<0. 01). However, compared with I/R group, the positive expression cells of P2X7 receptor protein in cerebral cortex and hippocampal CA1 area of NaHS + I/R group were significantly decreased ( P<0. 01). Conclusions H2S exerts the neuroprotective effect on focal cerebral ischemia/reperfusion injury in rats, and the protective mechanism might be associated with down-regulating the expression of P2X7 receptor protein in brain tissue.