3-硝基丙酸预处理对大鼠局灶性脑缺血Bcl-2和Bax mRNA表达的影响

Effects of 3-nitropropionic acid preconditioning on the Bcl-2 and Bax mRNA expressions following focal cerebral ischemia in rats

目的探讨3-硝基丙酸（3-NPA）预处理对大鼠局灶性脑缺血半暗带Bcl-2和BaxmRNA表达的影响。方法将大鼠腹腔注射3-NPA20mg／kg，3d后制作局灶性脑缺血再灌注模型；采用逆转录聚合酶链反应，观察3-NPA预处理对脑缺血再灌注1h、6h、12h、24h及48h额顶部皮质Bcl-2和BaxmRNA表达的影响，并与假手术组和缺血再灌注组比较。结果与假手术组比较，缺血再灌注组和3-NPA预处理组各时间点Bcl-2和BaxmRNA表达极显著增强（均P〈0．01）；与缺血再灌注组比较，3-NPA预处理组各时间点Bcl-2mRNA表达显著增强（均P〈0．05），再灌注12-48hBaxmRNA的表达显著降低（均P〈0．05）。结论增强Bcl-2的表达、抑制Bax的表达，可能是3-NPA预处理抑制细胞凋亡、诱导脑缺血耐受的机制之一。

Objective To investigate the involvement of Bcl-2 and Bax mRNA expressions in mitochondrial toxin 3-nitropropionic acid （3-NPA） induced ischemic tolerance to focal cerebral ischemia in rats. Methods Rats were administrated 3-NPA intraperitoneally at dose of 20 mg/kg 3 days prior to a 2 h middle cerebral artery occlusion followed by 1 h, 6 h, 12 h, 24 h and 48 h of reperfusion. The Bcl-2 and Bax mRNA expressions were measured by reverse transcriptase polymerase chain reaction and compared to the sham operation group and ischemic reperfusion group. Results Compared to the sham operation group, the ischemic reperfusion and 3-NPA pretreated groups exhibited an increase in Bcl-2 and Bax mRNA after reperfusion every time point of focal cerebral ischemia （ all P 〈 0.01 ）. The 3-NPA pretreated group was associated with a significant increase of Bcl-2 mRNA expression after reperfusion 1 h, 6 h, 12 h, 24 h, 48 h and reduction of Bax mRNA expression after reperfusion 12 ～48 h of focal cerebral ischemia compared with the ischemic reperfusion group （ all P 〈 0. 05 ）. Conclusion The mechanism of ischemic tolerance induced by 3-NPA may be related to up-regulation of Bcl-2 expression and down-regulation of Bax expression, which inhibit the apoptosis of neurons.