促红细胞生成素在缺氧缺血性脑病大鼠模型中的神经保护作用

Neuroprotective effect of erythropoietin on rat model of hypoxic-ischemic encephalopathy

目的制作新生大鼠缺氧缺血性脑病(hypoxic-ischemic encephalopathy,HIE)模型,研究重组人促红细胞生成素(erythropoietin,EPO)的脑保护作用和新生大鼠HIE肠道菌群多样性的变化,为临床应用EPO治疗新生儿缺氧缺血性脑病提供实验依据。方法选择7日龄SD大鼠制作HIE模型,随机分为HIE模型组、EPO实验组、对照组,免疫组织化学法观察巢蛋白(nestin)的表达变化,同时取各组大鼠粪便,用16s rRNA测序的方法观察肠道菌群的变化。结果各组大鼠同一时间点nestin的表达水平差异有显著性(P<0.05),对照组最低,EPO实验组最高,HIE模型组其次。HIE模型组的香农-威纳指数(Shannon-Wiener index)较对照组呈降低趋势。结论外源性给予EPO可以促进HIE新生大鼠模型的神经细胞生长,具有一定的保护作用,同时大鼠的肠道菌群多样性有所改变。

Objective To study the protective effect of recombinant human erythropoietin（ EPO） on brain and to explore the changes in the diversity of intestinal microbial flora in neonatal rats with hypoxic-ischemic encephalopathy（ HIE）by establishing a neonatal rat model of HIE,and to provide an experimental basis for clinical application of EPO in the treatment of neonatal HIE. Methods The HIE model was established in 7-day-old neonatal SD rats. The rats were randomly divided into the HIE model group,EPO-treated group and control group. The changes of nestin expression were detected by immunohistochemistry. Feces of the rats were collected to detect the changes in intestinal microbial flora by 16 s rRNA sequencing. Results The expressions of nestin at the same time point in each group were significantly different（ P〈0. 05）. The nestin level in the control group was the lowest,that in the EPO-treated group was the highest,and the HIE model group in between. The Shannon-Wiener index of the HIE model group showed a tendency to decrease compared with the control group. Conclusions Exogenous EPO can promote the growth of neural cells in neonatal rats with HIE,indicating a certain protective effect. Meanwhile,the diversity of intestinal microbial flora of the HIE neonatal rats is also changed.