血糖浓度对缺氧缺血新生大鼠脑内调控凋亡基因表达的影响  

Effect of blood glucose with different concentration on the expression of regulating cerebral apoptosis genes in neonatal rats with HI

作　　者：陈惠金[1] 张金凤[1] 钱龙华[1] 蒋明华[1] 吴圣楣[1] 陈冠仪[1] 

机构地区：[1]上海第二医科大学附属新华医院上海市儿科医学研究所,上海200092

出　　处：《临床儿科杂志》2004年第8期543-548,共6页Journal of Clinical Pediatrics

基　　金：国家自然科学基金资助项目(编号30070789)

摘　　要：目的通过观察缺氧缺血(HI)合并高或低血糖新生大鼠脑内一对调控凋亡基因Bcl?2和Bax基因的表达变化,从分子生物学角度评估葡萄糖对缺氧缺血脑保护效果。方法将7日龄SD新生大鼠分成正常对照组、H组、HI前低血糖组、HI前高血糖组以及HI后高血糖组,应用竞争性RT?PCR技术,分别于HI后0、2、6、12、24、48、7h及7d对各组新生大鼠脑内Bcl?2基因和Bax基因进行测定。结果正常情况下,Bcl?2基因和Bax基因在脑组织中无明显表达或仅有微弱表达。HI可引起这对调控凋亡基因的表达反应性增强,其中Bcl?2基因的表达高峰在HI后12h,Bax基因的表达高峰在HI后24h,在HI后48～72h,这一对基因的表达分别回落至低水平。血糖浓度对这一对基因的表达时相有明显影响。HI前高血糖组Bax基因的表达呈明显下调;Bcl?2基因的表达呈明显上调,其表达高峰较其余各组晚12h。HI前低血糖组Bax基因的表达呈明显上调;Bcl?2基因的表达则明显下调。HI后高血糖组的表达时相类似HI组,假手术组的基因表达则等同于正常组。结论结合本研究组已完成的脑细胞凋亡形态学结果,本研究进一步提示,通过上调Bcl?2基因和下调Bax基因的表达,高血糖在一定程度上抑制了HI后脑细胞的凋亡;低血糖则通过下调Bcl?2基因和上调Bax基因的表达,一定程度上加剧了HI后脑细胞的凋亡?Objective To explore the effect of blood glucose with different concentration on the expression of regulating cerebral apoptosis genes in neonatal rats with HI and to evaluate the neuroprotection of glucose against hypoxic ischemia.Methods 7- day- old neonatal rats were randomly divided into normal group,sham group,HI group,group with hypoglycemia before HI,group with hyperglycemia before HI,and group with hyperglycemia after HI.The expressions of Bcl-2 and Bax genes were determined with competitive RT- PCR at 0,2,6,12,24,48,72h and 7d after HI in neonatal rats of all six groups,respectively.Results No or weak expression of Bcl-2 and Bax genes were observed in normal situation.However,a reactive stronger expression of two genes could be induced by hypoxic ischemia.Their expressional peaks were at 12h after HI in Bcl-2 gene and at 24h after HI in Bax gene,and returned to lower levels at 48～72h after HI.The influence of glucose levels could be found on the expression of two genes.The expressions of Bcl-2 gene was observed to up- regulate in the group with hyperglycemia before HI and to down- regulate in the group with hypoglycemia before HI;and the expression of Bax was down- regulated in the group with hyperglycemia before HI and up- regulated in the group with hypoglycemia before HI.There was a similar time phase of expression between HI group and the group with hyperglycemia after HI.The expression of two genes in sham group was same as that in normal group.Conclusions Combined with the results of cerebral apoptosis morphology undertaken by the present research team,the present study further suggest that cerebral cell apoptosis induce by HI can be inhibited at certain extent by hyperglycemia through up- regulation of Bcl-2 gene expression and down- regulation of Bax gene expression;while cerebral apoptosis can be aggravated by hypoglycemia through up- regulation of Bax gene expression and down- regulation of Bcl-2 gene expression.It seems possible to maintain appropriate blood glucose level in high-ris

关 键 词：缺氧缺血 低血糖 高血糖 BCL-2基因 BAX基因 

分 类 号：R722.121[医药卫生—儿科]