摘要
目的通过观察依那普利(ACEI)对肾性高血压大鼠脑缺血再灌注后神经功能和一氧化氮合酶(NOS)的影响,探讨ACEI的脑保护机制。方法Wistar雄性大鼠56只,随机分为依那普利治疗组(Y,n=16)、高血压/缺血再灌注组(HIR,n=16)、正常血压/缺血再灌注组(IR,n=16)、假手术组(n=8);前三组再按时间点分为缺血2小时、再灌注24小时两个亚组,每组8只。采用狭窄肾动脉方法建立肾性高血压大鼠模型;采用线栓法造成大脑中动脉缺血再灌注模型。采用免疫组织化学方法检测脑组织内皮源性一氧化氮合酶(eNOS)、诱导性一氧化氮合酶(iNOS)、神经源性一氧化氮合酶(nNOS)的表达。结果Y组大鼠神经功能评分较HIR组和IR组降低(P<0.05);IR组神经功能评分低于HIR组(P<0.05);Y组与HIR组和IR组比较eNOS表达显著增高(P<0.05),nNOS和iNOS表达显著降低(P<0.05);HIR组与IR组比较,eNOS表达明显降低(P<0.05),而nNOS、iNOS表达明显增加(P<0.05)。结论肾性高血压可能通过增加nNOS和iNOS表达、抑制eNOS表达加重缺血再灌注后脑损伤;ACEI能够改善局灶性脑缺血大鼠的神经功能,上调脑组织eNOS表达,抑制nNOS、iNOS表达,提示这种抗高血压药可能对脑缺血再灌注损伤有脑保护作用。
Objective To study the effect of ACEI （enalapril） on NOS and the mechanism of neuro-protection in renal hypertension rats with focal cerebral ischemia-reperfusion. Methods 56 Wistar male rats were divided randomly into four groups： Enalapril group（Y,n=16）, hypertension ischemia-reperfusion group（HIR,n=16）, normaltension ischemia-reperfusion group（IR,n=16）, sham-operated group（N,n=8）. The former three groups were respectively divided into two subsets： ischemia for 2h （n=8）, reperfusion for 24h （n=8）. The model of renal hypertension rats was formed by constricted renovoscular. The model of cerebral ischemia reperfusion was developed by thread embolism method. The expression of eNOS, iNOS, nNOS were detected by immunohistochemistry. Results Compared with HIR and IR, the neurological evaluation of Y was lower（P〈 0.05）; with HIR, IR was lower （P〈0.05）. Compared with HIR and IR, the expression of eNOS were higher and iNOS, nNOS were lower in Y （P〈0.05）. Compared with HIR, the expression of eNOS were higher and iNOS, nNOS were lower in IR （P〈 0.05）.Conclusions Hypertension can inhibits the expression of eNOS, and upregulate the expression of nNOS,iNOS. ACEI （Enalapril） can improve the neurological function and upregulate the expression of eNOS, and inhibit the expression of nNOS, iNOS in rats with focal cerebral ischemia-reperfusion.
出处
《遵义医学院学报》
2007年第3期269-270,273,共3页
Journal of Zunyi Medical University
基金
遵义市科技局[2006]11号
