高血压对全脑缺血再灌注大鼠神经功能的影响及SP600125的干预作用  

Effect of SP600125on global cerebral ischemia / reperfusion in spontaneously hypertensive rats

作　　者：刘乐[1] 李建民[1] 赵雅宁[1] 常学优[1] 

机构地区：[1]河北联合大学康复医学院,河北唐山063000

出　　处：《中华高血压杂志》2012年第11期1043-1047,共5页Chinese Journal of Hypertension

基　　金：河北省科技厅课题(2009276103D-3)

摘　　要：目的探讨高血压对全脑缺血再灌注神经功能的影响及SP600125的干预作用。方法将12周龄42只雄性Wistar-Kyoto(WKY)大鼠随机分为对照组和WKY全脑缺血再灌注组(WKY+缺血再灌注组),同周龄46只雄性自发性高血压大鼠(SHR)随机分为高血压全脑缺血再灌注组(SHR+缺血再灌注组)、高血压全脑缺血再灌注加抑制剂组(抑制剂组)。抑制剂组于缺血前30min侧脑室注射c-Jun氨基末端激酶(JNK)抑制剂SP600125。应用四血管阻断法(Pulsinelli-4VO法)制备全脑缺血模型,脑缺血20min分再灌注24、48h两个时间点,电镜和光镜观察海马区神经细胞形态变化,再灌注48h应用神经功能学检测表评价运动和感觉功能。结果与WKY+缺血再灌注组对比,SHR+缺血再灌注组24、48h神经元细胞形态结构损伤随时间延长加重,神经元细胞存活密度降低(15.56±1.81比22.52±0.96,7.33±1.32比14.11±1.61,均P<0.05)。SHR+缺血再灌注组运动及感觉功能明显低于WKY+缺血再灌注组(4.79±0.93比7.79±0.72,4.42±0.72比6.42±0.65,均P<0.05)。与SHR+缺血再灌注组对比,抑制剂组24、48h神经元细胞形态结构明显改善,细胞存活密度增加(24.11±1.62比15.56±1.81,17.89±1.54比7.33±1.32),抑制剂组运动及感觉功能均明显提高(6.54±0.83比4.79±0.93,5.54±0.66比4.42±0.72,均P<0.05)。结论高血压加重脑缺血再灌注后神经功能的损伤,SP600125对高血压大鼠全脑缺血再灌注损伤有保护作用。Objective To investigate the effect of hypertension on global cerebral ischemia/reperfusion injury and the neuroprotective effect of SP600125 in spontaneously hypertensive rats（SHR）. Methods Forty two male Wist- ar-Kyoto （WKY} rats at 12 week-old were randomly divided into normal group （N group） and WKY ischemia/reper- fusion group （WKY＋IR group}. Forty-six 12-week-old male SHR were randomly divided into hypertension ische mia/reperfusion group （ SHR＋ IR group） and JNK（c-Jun N-terminal kinase） inhibitor SP600125 group（SP group）. SP600125 was injected into the lateral ventricle of rats 30 minutes before the ischemia in SP group. Whole brain is ehemia was induced by four-vessel occlusion. After 20 rain of ischemia the animals were reperfused for 24 and 48 hours respectively. The morphological changes of hippocampus neural cells were observed by light and electron microscopic and the motor and sensory function were evaluated by neurological examination scale at 48 h after surgery. Results Compared with WKY--IR group, morphological changes of hippocampus neural cells aggravated with time of ischemia and density of survival neurons decreased in SHR--IR group （15.56 ＋ 1.81 vs 22.52 ＋ 0.96, 7.33 ＋ 1.32 vs 14.11＋1.61, both P〈0.05）. The motor and sensory functions in SHRq-IR group were lower than those in WKY＋IR group （4.79±0.93 vs 7.79±0.72, 4.42±0.72 vs 6.42±0.65, both P〈0.05）. Compared with SHR＋IR group, in SP group, the morphological damage of neurons improved at 24, 48 h, the density of survival neurons increased （24.11±1.62 vs 15.56±1.81, 17.89±1.54 vs 7.33±1.32, both P〈0.05） and motor and sen sory functions were improved （6.54± 0.83 vs 4.79 ±0.93, 5.54±0.66 vs 4.42±0.72, both P〈0.05）. Conclusion Hypertension can aggravate the global ischemia/reperfusion injury and SP600125 has a neuroprotective effect in SHR.

关 键 词：脑缺血 高血压 再灌注损伤 SP600125 

分 类 号：R544.1[医药卫生—心血管疾病] R741[医药卫生—内科学]