高氧诱导下新生大鼠脑损伤的发生机制和前列腺素E1的干预作用  

Pathogenesis of brain injury induced by hyperoxia in newborn rats and intervention of prostaglandin E1

作　　者：王叶 王红[2] 朴丽贞[2] 杨山 张书剑 金正勇[1] WANG Ye;WANG Hong;PIAO Lizhen;YANG Shan;ZHANG Shujian;JIN Zhengyong(Department of Pediatrics,Affiliated Hospital,Yanbian University,Yanji 133000,China;Department of Pediatrics,China-Japan Union Hospital,Jilin University,Changchun 130033,China)

机构地区：[1]延边大学附属医院儿科,吉林延吉133000 [2]吉林大学中日联谊医院儿科,吉林长春130033

出　　处：《吉林大学学报（医学版）》2019年第6期1206-1211,I0015,共7页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金资助课题(81160083,81860279)

摘　　要：目的:探讨高氧诱导下新生大鼠脑损伤的发生机制,阐明前列腺素E1(PGE-1)通过内质网应激(ERS)途径发挥保护作用的机制,为高氧所致新生儿脑损伤的治疗提供相关理论依据。方法:90只新生Wistar大鼠随机分为对照组、高氧组和高氧+PGE-1组,每组30只。高氧组和高氧+PGE-1组大鼠放于高氧箱内,对照组大鼠置于同一室内常压条件下。自造模第1天开始,高氧+PGE-1组大鼠腹腔注射PGE-1,另外2组大鼠以同等剂量生理盐水替代。在高氧暴露第1、3和7天,每组随机选取10只大鼠检测体质量和脑组织含水量;HE染色观察3组大鼠脑组织形态表现;TUNEL染色观察3组大鼠脑细胞凋亡情况,计算细胞凋亡指数;Western blotting法检测各组大鼠脑组织中氨基末端蛋白激酶(JNK)和磷酸化JNK(p-JNK)表达量。结果:实验第1、3和7天,与同时间对照组比较,高氧组大鼠体质量明显降低(P<0.05),脑组织含水量增加(P<0.05);与高氧组比较,高氧+PGE-1组新生大鼠体质量明显升高(P<0.05),脑组织含水量降低(P<0.05)。HE染色,对照组大鼠大脑皮层细胞形态规则,排列有序,极少有炎性细胞的浸润、细胞的水肿;高氧组大鼠脑组织皮层细胞排列紊乱,大脑实质可见炎性细胞浸润,存在脑血管水肿;高氧+PGE-1组大鼠大脑皮层细胞排列整齐,细胞形态相对规则,脑实质炎性细胞数减少,水肿较高氧组减轻。TUNEL染色,对照组大鼠大脑组织以大脑皮层细胞为主,凋亡细胞少见,胞核呈均质蓝色;高氧组大鼠脑组织中胞核呈亮白色,为阳性凋亡细胞。与高氧组比较,同一时间高氧+PGE-1组凋亡细胞数明显减少;高氧组大鼠脑细胞凋亡指数高于高氧+PGE-1组和对照组(P<0.05)。高氧组大鼠脑组织中JNK和p-JNK表达量较对照组明显升高(P<0.05),高氧+PGE-1组大鼠脑组织中JNK和p-JNK表达量较高氧组明显降低(P<0.05)。结论:高氧导致新生大鼠脑损伤的发病机制可能与下调ESR相关Objective:To investigate the pathogenesis of brain injury induced by hyperoxia in the newborn rats,to elucidate the mechanism of the protect effect of prostaglandin E1(PGE-1)through endoplasmic reticulum stress(ERS)pathway,and to provide the relevant theoretical basis for the treatment of brain injury of the newborns induced by hyperoxia.Methods:Ninety newborn Wistar rats were randomly divided into control group,hyperoxia group and hyperoxia+PGE-1 group,and there were 30 rats in each group.The rats in hyperoxia group and hyperoxia+PGE-1 group were placed in the hyperoxia box;the rats in control group were placed under the same room pressure conditions.From the 1st day of modeling,the PGE-1 was intraperitoneally injected into the rats in hyperoxia+PGE-1 group.The rats in the other two groups were injected with the same dose of normal saline.On the 1st,3rd and 7th days of hyperoxia exposure,10 rats in each group were randomly selected to detect the body weights and water contents of brain tissue;the morphology of brain tissue of the rats in three groups was observed by HE staining;the apoptosis of brain cells of the rats in three groups was observed by TUNEL staining,and the apopotic indexes were caculated;the expression amount of c-Jun N-terminal protein kinase(JNK)and phosphorylated JNK(p-JNK)proteins in brain tissue of the rats in three groups were detected by Western blotting method.Results:On the 1st,3rd and 7th days,the body weights of the rats in hyperoxia group were significantly lower than those in control group(P<0.05);the water contents in brain tissue of the rats in hyperoxia group were significantly higher than those in control group(P<0.05);compared with hyperoxia group,the body weights of the rats in hyperoxia+PGE-1 group were increased(P<0.05),and the water contents in brain tissue were decreased(P<0.05).The HE staining results showed that the cerebral cortex cells of the rats in control group were regular in shape and arranged in order,with little infiltration of inflammatory cells and edema of cel

关 键 词：高氧脑损伤 内质网应激 前列腺素E1 新生大鼠 

分 类 号：R742.8[医药卫生—神经病学与精神病学]