高氧对新生大鼠脑组织中NRP-cGMP信号通路的影响

doi:10.13481/j.1671-587x.20180304

摘要/Abstract

摘要： 目的：构建高氧诱导新生大鼠脑损伤模型，探讨高氧对新生大鼠脑组织中钠尿肽受体-环磷酸鸟苷（NRP-cGMP）信号通路的影响。方法：60只新生Wistar大鼠随机分为对照组和高氧模型组，每组30只。高氧模型组大鼠置于自制高氧箱内（氧浓度>85%）吸入氧气7 d；对照组大鼠置于同一室内常压空气环境下，持续吸入空气7 d。高氧暴露1、3和7d时，每组随机选取10只大鼠取脑组织，检测2组大鼠体质量；HE染色法观察2组大鼠脑组织形态表现；透射电镜下观察2组大鼠脑组织超微结构；Western blotting法检测2组大鼠脑组织中钠尿肽受体A（NPR-A）和钠尿肽受体B（NPR-B）表达水平；ELISA法测定2组大鼠脑组织中cGMP水平。结果：高氧暴露1、3和7d时，高氧模型组大鼠体质量明显低于对照组（P<0.05）。HE染色，高氧暴露3d时，光镜下可见高氧模型组大鼠海马锥体细胞体积缩小，排列稀疏；高氧暴露7d时，高氧模型组大鼠海马细胞出现深染皱缩，细胞与周围分界不清。电镜下形态表现，高氧暴露3d时，高氧模型组大鼠线粒体双层膜结构破坏，少许嵴消失，线粒体及突触数量减少；高氧暴露7d时破坏进一步加重。Western blotting检测，高氧暴露1、3和7d时，高氧模型组大鼠脑组织中NPR-A表达水平高于对照组（P<0.05），但仅高氧暴露1 d时大鼠脑组织中NPR-B水平高于对照组（P<0.05）。ELISA法检测，高氧暴露1、3和7d，高氧模型组大鼠脑组织中cGMP水平均高于对照组（P<0.05）。结论：NRP-cGMP信号通路参与了高氧诱导脑损伤的发生。

关键词: 脑损伤, 环磷酸鸟苷, 高氧, 大鼠, Wistar, 钠尿肽受体

Abstract: Objective: To construct the brain tissue damage models of newborn rats induced by hyperoxia,and to explore the effect of hyperoxia on the natriuretic peptide receptor-cyclic guanosine monophosphate(NRP-cGMP) signaling pathway in brain tissue of the newborn rats. Methods: A total of 60 newly born Wistar rats were divided into control group and hyperoxia model group,and there were 30 rats in each group. At the 1st,3rd and 7th days after hyperoxia exposure,the brain tissues of 10 rats randomly selected from each group were gotten,and the body weights of the rats in two groups were detected.HE staining was used to observe the morphology of brain tissue of the rats in two groups;the ultrastructures of brain tissue of the rats in two groups were observed under transmission electron microscope.Western blotting method was used to detect the expression levels of natriuretic peptide receptor A (NPR-A) and natriuretic peptide receptor B (NPR-B) in brain tissue of the rats in two groups.ELISA method was used to determine the levels of cGMP in brain tissue of the rats in two groups. Results: The body weight of the rats in hyperoxia model group was significantly lower than that in control group at the 1st,3rd and 7th days after hyperoxia exposure(P<0.05).The HE staining results showed that at the 3rd day after hyperoxia exposure,the volume of the hippocampal pyramidal cells of the rats in hyperoxia model group was reduced, and the arrangement was sparse;at the 7th day after hyperoxia exposure,the hippocampal cells showed deep staining and shrinkage, and the cell boundaries were not clear. Under electron microscope,at the 3rd day after hyperoxia exposure, the mitochondrial double membrane structure of the rats in hyperoxia model group was destroyed,a few crest disappeared,and the number of mitochondria and synapses was decreased; the above damage conditions were aggravated at the 7th day after birth.The Western blotting results showed that at the 1st,3rd and 7th days after hyperoxia exposure,the expression level of NPR-A in brain tissue of the rats in hyperoxia model group was higher than that in control group(P<0.05).But only at the 1st day after hyperoxia exposure,the expression level of NPR-B in brain tissue of the rats in hyperoxia model group was higher than that in control group(P<0.05).The ELASA results showed that at the 1st,3rd and 7th days after hyperoxia exposure, the level of cGMP in brain tissue of the rats in hyperoxia model group was higher than that in control group(P<0.05). Conclusion: NRP-cGMP signaling pathway is involved in the occurrence of brain injury induced by hyperoxia.

Key words: hyperoxia, brain injury, cyclic guanosine monophosphate, natriuretic peptide receptor, rat,Wistar

中图分类号:

R338

张书剑, 张有辰, 李慧文, 金正勇. 高氧对新生大鼠脑组织中NRP-cGMP信号通路的影响[J]. 吉林大学学报(医学版), 2018, 44(03): 477-482.

ZHANG Shujian, ZHANG Youchen, LI Huiwen, JIN Zhengyong. Effect of hyperoxia on NRP-cGMP signaling pathway in brain tissue of newborn rats[J]. Journal of Jilin University Medicine Edition, 2018, 44(03): 477-482.

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