胰岛素样生长因子-1对缺氧缺血性脑损伤新生大鼠大脑皮质中内质网应激相关因子表达的影响

Effects of insulin-like growth factor 1 on the expression of endoplasmic reticulum stress-related factors in the cerebral cortex of newborn rats with hypoxic ischemic brain damage

[目的]观察胰岛素样生长因子-1(IGF-1)对缺氧缺血性脑损伤(HIBD)新生大鼠大脑皮质中内质网应激相关因子葡萄糖调节蛋白(GRP)和C/EBP同源蛋白(CHOP)表达的影响.[方法]取足月新生Wistar大鼠(7d龄),随机分为正常对照组、模型对照组和重组胰岛素样生长因子-1(rh-IGF-1)组,后两组参照Rice方法制作HIBD新生大鼠模型.之后rh-IGF-1组立即腹腔注射给予rh-IGF-1,正常对照组和模型对照组腹腔注射给予等量生理盐水.各组大鼠分别于缺氧后24,48h取大脑组织,采用HE染色法和原位末端标记法观察大脑皮质神经元的病理改变及细胞凋亡情况,利用免疫组织化学染色法检测各组大鼠大脑皮质GRP78,CHOP的表达水平.[结果]模型对照组脑组织中GRP78,CHOP表达及凋亡细胞数较正常对照组明显增加(P<0.05),rh-IGF-1组GRP78,CHOP表达及凋亡细胞数较模型对照组明显减少(P<0.05).[结论]IGF-1通过下调GRP78,CHOP表达抑制神经细胞凋亡,从而减轻缺氧缺血所致的脑组织损伤.

OBJECTIVE To observe the effects of insulin-like growth factor 1 （IGF-1） on the expression of endoplasmic reticulum stress-related factors glucose-regulated protein（GRP） and C/EBP homologous protein （CHOP） in the cerebral cortex of newborn rats with hypoxic ischemic brain damage（HIBD）. METHODS Neonatal Wistar rats （7 days old） were randomly divided into normal control group, model control group and rh-IGF-1 group. A neonatal rat model of HIBD was established by Rice method in the model, control and rh-IGF-1 groups. The rats in the rh-IGF-1 group were intraperitoneally injected with rh-IGF-1 （20 t^g/kg） immediately after HIBD, and the other two groups were intraperitoneally injected with an equal volume of normal saline. Brain tissues were collected at time of 24 and 48 hour after HIBD. The pathological changes and apoptosis of neurons were observed by HE staining and terminal deoxynucleotide transferase （TdT）- mediated dUTP nick-end labeling method. The expression of GRP78 and CHOP was determined by immuno- histochemical staining. RESULTS As compared with the normal control group, the expression of GRP78 and CHOP and the number of apoptotic cells were increased in the model control grouo （P〈0.05）, and the expression of GRP78 and CHOP and the number of apoptotic ceils were decreased in the rh-IGF-1 group than those in the model control group （P〈 0.05）. CONCLUSION IGF-1 inhibited nerve cells apoptosis by down-regulating the expression of GRP78 and CHOP to reduce ttIBD.