缺氧缺血性脑损伤新生大鼠脑神经细胞凋亡及脑组织中Rho GDP解离抑制因子和Bcl-2表达的变化  

Changes of neuronic apoptosis, Rho GDP dissociation inhibitor 2 and Bcl-2 in brain tissue of neonatal rats with hypoxic-ischemic brain damage

作　　者：顾卉[1] 纪莲[1] 由凯[2] 梁爽[3] 袁正伟[1] 

机构地区：[1]中国医科大学附属盛京医院实验研究中心,沈阳110004 [2]中国医科大学附属盛京医院新生儿科,沈阳110004 [3]美国明尼苏达州明尼苏达大学实验病理系,明尼艾波利斯市55455

出　　处：《中国小儿急救医学》2011年第6期536-538,共3页Chinese Pediatric Emergency Medicine

摘　　要：目的研究RhoGDP解离抑制因子（Rho GDP dissociation inhibitor 2，RhoGDI2）mRNA及Bcl-2mRNA的表达在缺氧缺血性脑损伤（hypoxic-ischemic brain damage，HIBD）中的作用和机制。方法30只新生7日龄SD大鼠按照完全随机化方法分为假手术组及HIBD6h和48h组，每组10只。采用流式细胞仪检测脑细胞凋亡情况，并用Real—timeRT—PCR方法测定脑组织中RhoGDI2和Bcl-2mRNA表达水平。结果（1）新生大鼠HIBD后48h结扎侧大脑半球脑水肿明显。（2）HIBD6h出现典型的凋亡细胞峰，细胞凋亡率为（1．40±0．12）％。HIBD48h凋亡峰更为明显，细胞凋亡率达到（15．86±0．98）％。缺氧缺血后与假手术组相比，差异有统计学意义（P〈0．01）。（3）假手术组大鼠RhoGDI2和Bcl-2mRNA表达水平较高（4．12±0．74、2．55±0．65），在HIBD6h后二者表达开始下降（3．19±0．77、1．96±0．36），48h降低更加明显（1．04±0．18、1．06±0．17），与假手术组比较，HIBD各时间点RhoGDI2和Bcl-2mRNA的表达均明显降低，差异有统计学意义（P〈0．01）。（4）缺氧缺血后各时间点RhoGDI2mRNA的表达和Bcl-2mRNA的表达呈正相关（r=0．831，P〈0．05）。结论脑缺氧缺血后，随着凋亡的出现，RhoGDI2和Bcl-2mRNA表达水平降低，提示RhoGDI2表达失衡可能通过Bcl-2参与新生大鼠HIBD中凋亡的发生。Objective To investigate the effect of Rho GDP dissociation inhibitor 2 （RhoGDI2） and Bcl-2 in pathogenesis of hypoxic-ischemic brain damage （HIBD）. Methods Neonatal 7-day-old Sprague Dawley rats were randomly divided into sham-operation control group, HIBD 6 h group and HIBD 48 h group （ n = 10 per group）. The apoptosis rate of brain cell was measured by flow cytometer and the expression of RhoGDI2 mRNA and Bcl-2 mRNA were detected by Real-time RT-PCR. Results （ 1 ） The ligated cerebral hemisphere of neonatal rats showed obvious edema at 48 h after hypoxia-ischemia. （ 2 ） Apoptotic cell appeared at 6 h in HIBD group,the apoptosis rate was （ 1.40 ±0. 12） %. The apoptosis rate obviously increased to （ 15.86 ±0.98 ） % at 48 h after HIBD, which showed a significant increase compared to sham-operation control group （ P 〈 0.01 ）. （ 3 ） The expressions of both RhoGDI2 mRNA and Bcl-2 mRNA were 4. 12 ±0. 74 and 2. 55±0. 65 respectively in sham-operation control group. In HIBD group, the expressions of both RhoGDI2 mRNA and Bcl-2 mRNA began to decrease at 6 h after HIBD （3. 19±0. 77,1.96±0. 36） and decreased furthermore at 48 h after HIBD （ 1.04±0. 18,1.06 ±0. 17 ）. The differences of expression levels among three groups were statistically significant （P 〈 0. 01 ）. （4） The expression of RhoGDI2 mRNA positively correlated with the expression of Bcl-2 mRNA （ r = 0. 831, P 〈 0. 05 ）. Conclusion With the emerging of apoptosis after HIBD, the expressions of both RhoGDI2 mRNA and Bcl-2 mRNA are decreased. The imbalance of expression of RhoGDI2 is involved in pathogenesis of HIBD by regulating Bcl-2 expression.

关 键 词：缺氧缺血性脑损伤 RHO GDP解离抑制因子 Bcl-2 凋亡 大鼠 新生 

分 类 号：R722.1[医药卫生—儿科]