摘要
目的 研究三磷酸腺苷敏感性钾通道(KATP)开放剂对大鼠脑缺血再灌注后神经元凋亡和天冬氨酸特异性半胱氨酸蛋白酶(caspase)-8 表达的影响.方法 200只Wistar雄性大鼠随机分为假手术组、对照组、KATP开放剂预处理组(开放剂组)及KATP开放剂+阻断剂预处理组(阻断剂组).应用线栓法制备大鼠大脑中动脉缺血再灌注模型,应用原位末端标记法(TUNEL)、免疫组化染色、逆转录-聚合酶链反应(RT-PCR)技术检测脑缺血再灌注后各组脑组织凋亡细胞数和caspase-8 mRNA及蛋白的表达.结果 (1)缺血再灌注12 h、24 h、48 h、72 h各时间点凋亡细胞数,开放剂组较对照组和阻断剂组显著减少(P＜0.05～0.01),阻断剂组与对照组间各时间点差异无统计学意义.(2)缺血再灌注12 h、24 h、48 h、72 h各时间点caspase-8蛋白表达,开放剂组显著低于对照组和阻断剂组(P＜0.05～0.01),阻断剂组与对照组间各时间点差异无统计学意义.(3)缺血再灌注各时间点caspase-8 mRNA表达,开放剂组均显著低于对照组和阻断剂组(均P＜0.01), 阻断剂组与对照组各时间点相比差异无统计学意义.结论 KATP开放剂能显著减少脑缺血再灌注后神经元凋亡和caspase-8 mRNA及蛋白的表达;KATP开放剂可能通过抑制死亡受体通路发挥脑保护作用.
Objective To study the effect of ATP sensitive potassium channel(KATP)opener on neuronal apoptosis and the expression of caspase-8 mRNA and protein in rats following cerebral ischemia-reperfusion.Methods 200 male Wistar rats were randomly divided into sham-operated group,control group,KATP opener precondition group(KATP opener group)and KATP opener and blocker precondition group(KATP blocker group).The middle cerebral artery ischemia-reperfusion models were established by using the intraluminal suture occlusion method.Neuronal apoptosis were detected by TUNEL staining,the expression of caspase-8 mRNA and protein were detected by immunohistochemical staining and RT-PCR methods.Results(1)The numbers of apoptotic cells in KATP opener group at 12 h,24 h,48 h,72 h after cerebral ischemia-reperfusion were significantly less than those in control group and KATP blocker group(P<0.05~0.01),there was no difference between control group and KATP blocker group at all times.(2)The expression of caspase-8 protein in KATP opener group at 12 h,24 h,48 h,72 h were significantly less than those in control group and KATP blocker group(P<0.05~0.01),there was no difference between control group and KATP blocker group at all times.(3)The expression of caspase-8 mRNA in KATP opener group at all times were significantly less than those in control group and KATP blocker group(all P<0.01),there was no difference between control group and KATP blocker group at all times.Conclusions KATP opener can significantly decrease neuronal apoptosis and the expressions of caspase-8 mRNA and protein following cerebral ischemia-reperfusion.KATP opener plays a neuroprotective role by inhibiting death receptor signaling pathway following cerebral ischemia-reperfusion.
出处
《临床神经病学杂志》
CAS
北大核心
2007年第5期364-367,共4页
Journal of Clinical Neurology
基金
辽宁省自然科学基金资助项目(20052097)
