地塞米松对脑缺氧缺血新生大鼠bcl-x及bax基因表达的调节

The regulatory effects of dexamethasone on mRNA expression of bcl-x and bax in neonatal rats with cerebral hypoxia-ischemia

目的 探讨地塞米松 (DEX)预处理对缺氧缺血 (HI)新生大鼠脑保护作用的可能机制。方法 通过建立新生大鼠缺氧缺血性脑病 (HIE)动物模型 ,应用快速竞争性RT PCR技术 ,分别对HI、DEX预处理后于HI、缺氧结束后即刻予DEX、DEX加假手术、正常对照 5组 (每组 40只鼠 )动物的实验侧大脑组织中bcl x (bcl xl和bcl xs)、baxmRNA的表达进行半定量分析。结果 脑HI后bcl xs、baxmRNA的表达明显增强 ,并在HI后 2 4h左右达高峰 (bcl xs 1.5 2± 0 .17,bax 1.43± 0 .17) ,在脑HI后 2～ 72h ,DEX预处理组bcl xs、baxmRNA的表达水平 (bcl xs 0 .0 3± 0 .0 5～ 0 .19± 0 .2 3,bax 0 .0 2± 0 .0 3～ 0 .13± 0 .2 1)显著低于HI组 (bcl xs 0 .14± 0 .0 6～ 1.5 2± 0 .17,bax 0 .0 9± 0 .0 3～ 1.43± 0 .17) (P <0 .0 1) ,而HI后给予DEX组其bcl xs、baxmRNA的表达量 (bcl xs 0 .13± 0 .0 7～ 1.5 3± 0 .18;bax 0 .0 7±0 .0 5～ 1.47± 0 .10 )与HI组之间的差异无显著性 (P >0 .0 5 )。DEX及HI对bcl xlmRNA的表达无明显影响。结论 脑HI可诱导bcl xs、baxmRNA过表达 ,这种过表达在脑HI后细胞凋亡的调控过程中可能起着重要作用。DEX预处理可通过抑制bcl xs、baxmRNA的过表达起到抗细胞凋亡的作用。

Objective To explore the possible mechanisms of the neuroprotective effect of dexamethasone(DEX) on neonatal rats with cerebral hypoxia ischemia. Methods The rapid competitive reverse transcriptase PCR was used to analyze the expression of bcl x (bcl xl and bcl xs) and bax mRNA at ipsilateral cerebral hemisphere semi quantitatively in the neonatal rat model of hypoxia ischemia(HI group), DEX treatment prior to hypoxia ischemia(DH group), DEX treatment immediately following hypoxia ischemia(HD group), DEX treatment prior to sham operation and normal controls, respectively. Results The expressions of bcl x and bax mRNA in the ipsilateral hemisphere following cerebral hypoxia ischemia increased significantly, and reached the peak level at 24 h (bcl x was 1.52±0.17 and bax was 1.43±0.17). During 2 h to 72 h following hypoxia ischemia, the expressions of bcl x and bax mRNA in DH group (bcl xs were significantly lower than those in HI group (bcl xs: 0.03±0.05～ 0.19±0.23 versus 0.14±0.06～1.52±0.17, and bax: 0.02±0.03～0.13±0.21 versus 0.09±0.03～ 1.43± 0.17, respectively, P<0.01). While there were no significant differences in the expressions of bcl xs and bax mRNA between HD group (0.13±0.07～1.53±0.18 and 0.07±0.05～1.47±0.10, respectively) and HI group (P>0.05). DEX and HI had no evident effect on the expression of bcl x mRNA. Conclusion Cerebral HI could induce the overexpressions of bax and bcl x mRNA, which could play an important role in the regulation of apoptosis following cerebral HI. Pretreatment with DEX could exert the anti apoptotic role by the down regulation of bax and bcl xs gene expressions.