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目的研究ATP敏感钾通道(KATP)调节剂预处理对沙鼠全脑缺血再灌注(ischemia-reperfusion,I-R)损伤中KATP亚基表达的影响。方法采用夹闭双侧颈总动脉(10 min)、再灌注60 min建立沙鼠I-R模型,将48只沙鼠随机分成8组:假手术组,I-R组,I-R+二氮嗪组,I-R+5-羟葵酸(5-Hydroxydecanoate,5-HD)组,I-R+二氮嗪+5-HD组,I-R+吡那地尔组,I-R+格列本脲组,I-R+吡那地尔+格列本脲组。各组分别预给予相应KATP开放剂与阻断剂,脑组织提取总RNA进行逆转录多聚酶链式反应(RT-PCR),观察药物预处理对KATP亚基mRNA表达的变化。结果与假手术组比,I-R组Kir6.1 mRNA明显增加;与I-R组比较,I-R+二氮嗪组Kir6.1 mRNA明显增加,而I-R+格列本脲组明显降低。与假手术组相比,SUR2 mRNA表达在I-R和各药物处理组明显增加,I-R和各药物处理组间没有明显差异。与假手术组比较,SUR1mRNA无论是在缺血组,还是在药物预处理组沙鼠脑内的表达均没有差异。结论二氮嗪可明显增加Kir6.1 mRNA的表达,Kir6.1亚基在脑缺血保护中发挥着重要的作用;在脑缺血再灌注下,KATP开放剂和阻断剂不影响SUR1和SUR2 mRNA的表达。
Objective To investigate the effect of ATP-sensitive potassium channel (KATP) preconditioning on the expression of KATP subunit in global cerebral ischemia-reperfusion (I-R) injury in gerbils. Methods The gerbil IR model was established by occluding bilateral common carotid arteries (10 min) and reperfusion for 60 min. 48 gerbils were randomly divided into 8 groups: sham operation group, IR group, I-R + diazoxide group, I R + 5-HD group, I-R + diazoxide + 5-HD group, I-R + pinacidil group, I- -R + pinacidil + glyburide group. The corresponding KATP openers and blockers were pre-given in each group. The total RNA was extracted from the brain tissues for reverse transcription polymerase chain reaction (RT-PCR) to observe the change of KATP subunit mRNA expression. Results Compared with the sham-operated group, the expression of Kir6.1 mRNA in I-R group was significantly increased. Compared with I-R group, the expression of Kir6.1 mRNA in I-R + diazoxide group was significantly increased, while the I-R + glibenclamide group was significantly decreased. Compared with the sham operation group, the expression of SUR2 mRNA in I-R and each drug treatment group was significantly increased, there was no significant difference between I-R and each drug treatment group. Compared with the sham operation group, there was no difference in the expression of SUR1 mRNA in the brain of the ischemic group and the drug pretreatment group. Conclusion Diazoxide can significantly increase the expression of Kir6.1 mRNA, Kir6.1 subunit plays an important role in cerebral ischemia protection; under cerebral ischemia and reperfusion, KATP openers and blockers do not affect SUR1 and SUR2 mRNA expression.