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ATP敏感性钾通道(KATP)开放剂对脑缺血/再灌注大鼠谷氨酸受体1a和谷氨酸转运体1的影响

Impact of cromakalim pre-conditioning on mGluR1a and GLT-1 expression in rats with cerebral ischemia-reperfusion injury

摘要目的 研究ATP敏感性钾通道(KATP)开放剂克罗卡林对大鼠脑缺血/再灌注后脑梗死体积、代谢型谷氨酸受体1α(mGluRlα)和谷氨酸转运体1(GLT-1或者EAAT-2)的影响.方法 雄性Wistar大鼠按序号随机分为假手术组(A组)、缺血/再灌注脑缺血对照组(middle cerebral artery occlusion MCAOB,B组)、MCAO+ATP敏感性钾通道(KATP)开放剂克罗卡林组(C组).应用线栓法建立大鼠大脑中动脉闭塞再灌注(middle cerebral artery occlusion,MCAO)模型,大鼠脑缺血/再灌注24 h后,Bederson法评价动物的神经行为功能,氯化三苯基四氮唑(TTC)染色观察脑梗死体积,免疫组化测定谷氨酸受体1α(mGluR1α)和GLT-1.结果 脑缺血/再灌注24 h后,动物均表现神经行为功能障碍,大鼠神经行为功能评分C组(2.23±0.11)较B组(2.61±0.19)明显改善,差异有统计学意义(P<0.05);缺血侧出现脑梗塞病灶,脑梗死体积C组(138.3±29.9)较B组(182.5±34.5)显著减小,差异具有统计学意义(P<0.05);B组mGluR1α吸光度(0.293±0.009)与A组mGluR1α吸光度(0.183±0.008)相比,吸光度明显增加,差异有统计学意义(P<0.05)、B组GLT-吸光度(0.147±0.009)与A组GLT-吸光度(0.255±0.009)相比,吸光度明显减少,差异有统计学意义(P<0.05);C组mGluR1α吸光度(0.227±0.009)与B组mGluR1α吸光度(0.293±0.009)相比,其吸光度明显减小,差异有统计学意义(P<0.05)、C组GLT-1吸光度(0.212±0.008)与B组GLT-1吸光度(0.147±0.009)相比明显增大,差异有统计学意义(P<0.05).结论 预防性应用克罗卡林可能通过减少mGluR1α表达,增强GLT-1表达,减少谷氨酸堆积,减小脑梗死体积,从而减轻脑组织缺血/再灌注损伤.

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abstractsObjective To study the effects of ATP sensitive potassium channel opener, cromakalim, on cerebral infarction volume, metabotropic glutamate receptor 1 ( mGluR1α ), glutamate transporter 1 ( GLT-1 ) after cerebral ischemic reperfusion. Methods Male Wistar rats were randomized into three groups (n=20): sham-operated group, MCAO group and MCAO + cromakalim group.Intraluminal thread method was applied to establish the middle cerebral artery occlusion (MCAO) reperfusion model. The nervous behavioral function was evaluated with Bederson's test, the cerebral infarction volume was measured with tetrazolium chloride staining,mGluR1α and GLT-1 were detected using immunohistochemistry method 24h after reperfusion. Results At the 24 h after cerebral ischemic reperfusion injury, neurological behavioral malfunction appeared in all the mice, the score of neurological behavioral function in group C (2.23 ±0.11 )was improved compared with that in group B (2.61 ±0. 19) (P<0.05); Focus of cerebral infarction was found in the ischemic hemisphere of the brain, the cerebral infarction volume in group C ( 138.3±29.9 )was significantly reduced compared with that in group B(182.5±34.5) (P<0.05); the absorbance of mGluR1α in group B(0.293±0.009) was increased compared with that in group A (0.183±0.008), the absorbance of GLT-1 in group B(0.147±0.009 ) was increased compared with group A(0.255±0.009 )(P <0.05 ), the absorbance of mGluR1α in group C (0.227±0.009) was decreased compared with group B (0.293±0.009)(P <0.05 ); the absorbance of GLT-1 in group C(0.212±0.008)was increased compared with group B(0. 147±0.009)(P<0.05). Conclusion Reducing ischemia reperfusion injury through the preventive use of Cromakalim may be related to decreasing the expression of mGluR1α,increasing the expression of GLT-1, inhibiting the accumulation of glutamic acid, and reducing the cerebral infarction volume.

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分类号 R74
栏目名称 论著
DOI 10.3760/cma.j.issn.1673-4378.2010.02.012
发布时间 2010-06-28
基金项目
山东省科技攻关计划
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