rhIGF-1对缺氧缺血性脑损伤新生大鼠Cyt-C及caspase-3表达的影响

Effect of rhIGF-1 on cytochrome C and caspase-3 expression in neonatal rats with hypoxic-ischemic brain damage in vivo

摘要:

目的：探讨人重组胰岛素样生长因子-1（rhIGF-1）对缺氧缺血性脑损伤（HIBD）新生大鼠细胞色素（Cyt-C）及 caspase-3 表达的影响。方法：90只新生Spargue-Dawley 大鼠随机分为正常对照、HIBD 和 HIBD+rhIGF-1 组。按照Rice-Vannucci 法制作HIBD模型，HIBD+rhIGF-1 组于HI后即刻予腹腔注射rhIGF-1（0.2 mg/kg）。应用 RT-PCR 和 Western blot技术于HI后24 h、48 h、72 h 分别检测 Cyt-C及caspase-3的mRNA及蛋白表达。结果：HIBD组各时间点的Cyt-C mRNA 和caspase-3 mRNA 表达较正常对照组均明显升高，HIBD+rhIGF-1 组的表达则较正常对照组升高、但较 HIBD 组降低，3组之间的差异具有统计学意义（P<0.01）。HIBD 组的 Cyt-C 和 caspase-3 蛋白表达在各时间点均明显高于正常对照组，HIBD+rhIGF-1 组的表达则较正常对照组升高、但较 HIBD 组降低，3组之间的差异具有统计学意义（P<0.01）。Peason 相关分析显示，HIBD 组和 HIBD+rhIGF-1 组的 CytC 与 caspase-3 mRNA和蛋白表达为直线相关关系。结论：rhIGF-1 可能通过抑制 Cyt-C 释放、减少 caspase-3 表达，从而对新生大鼠 HIBD 发挥保护作用。［中国当代儿科杂志，2010，12(12)：963-966］

Abstract:

OBJECTIVE: To study the effect of rhIGF-1on the mRNA and protein expression of cytochrome C (Cyt-C) and caspase-3 in neonatal rats with hypoxic-ischemic brain damage (HIBD). METHODS: Ninety neonatal Sprague-Dawley rats were randomly divided into three groups: normal control, HIBD, and HIBD+rhIGF-1 (rhIGF-1 was given intraperitoneally right after HI). Rat HIBD model was prepared according the Rice-Vannucci method. RT-PCR and Western blot methods were used to measure the mRNA and protein expression of Cyt-C and caspase-3 24, 48 and 72 hrs after HI (n=10 each time point). RESULTS: At all time points, both Cyt-C mRNA and caspase-3 mRNA expression levels in the HIBD group increased compared with those in the normal control group, and those in the HIBD+rhIGF-1 group also increased compared with that in the normal control group but decreased compared with that in the HIBD group. There were statistical significances among the three groups (P<0.01). At all time points, the changes of both Cyt-C and caspase-3 protein expression in the three groups were similar to those of the mRNA expression: both Cyt-C and caspase-3 protein expression levels increased in the HIBD group compared with those in the normal control group, and those in the HIBD+rhIGF-1 group also increased compared with those in the normal control group but decreased compared with those in the HIBD group. There were statistical significances among the three groups (P<0.01).Pearson correlation analysis showed that mRNA and protein expression of Cyt-C were positively correlated to casapse-3 mRNA and protein expression in the HIBD and the HIBD+rhIGF-1 groups. CONCLUSIONS: rhIGF-1 may inhibit the Cyt-C release and caspase-3 expression, and thus provides neuroprotection against HIBD in neonatal rats.［Chin J Contemp Pediatr, 2010, 12 (12):963-966］