Developmental endothelial locus-1 enhances ER calmodulin expression,mitigates ER stress,suppresses inflammation,and attenuates neuronal apoptosis  

Del-1促进SERCA2表达抑制ER应激、炎症和神经细胞凋亡保护小鼠SCI

作　　者：Hao Wang Kangxue Chen Yuyan Zhang Kuijun Jiang Zhonglei Sun 王浩;陈康雪;张雨焱;蒋奎军;孙中磊(简阳市中医医院,四川简阳641400;四川泰康医院,四川成都610500)

机构地区：[1]Jianyang Chinese Medicine Hospital,Jianyang 641400,Sichuan,China [2]Sichuan Taikang Hospital,Chengdu 610500,Sichuan,China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2024年第9期795-804,共10页中国药学（英文版）

基　　金：National Key Research and Development Plan of China(Grant No.2016YFC1101503)。

摘　　要：This study aimed to investigate the impact of developmental endothelial locus-1(Del-1)on sarcoplasmic reticulum Ca^(2+)ATPase 2(SERCA2)and its potential effects on spinal cord injury(SCI).A total of 48 mice were randomly assigned to the sham group,SCI group,and SCI+CE group.Each group was further divided into two subgroups.The Del treatment subgroup received tail-vein injections of Del-1(1μg/d)for a consecutive week,while the other group was injected with an equivalent volume of normal saline.After 1 week of experimentation,the mice were euthanized,and the spinal cord was extracted for further analysis.Initially,the impact of Del-1 on SERCA2 in the spinal cord was assessed using western blotting analysis.Subsequently,the effects of Del-1 on stress,inflammation,and apoptosis in the endoplasmic reticulum(ER)of SCI mice were analyzed through Western blotting analysis and fluorescent TUNEL.Finally,the study utilized Western blotting analysis and fluorescent TUNEL analysis to examine the consequences of Del-1 blocking SERCA2 on ER stress,inflammation,and apoptosis in mice.The results revealed that Del-1 treatment significantly increased the expression of SERCA2 in the spinal cord(P<0.01)and mitigated SCI-induced ER stress,inflammation,and neuronal apoptosis(P<0.01).Blocking SERCA2 expression in the spinal cord of SCI mice promoted ER stress,inflammatory response,and neuronal cell apoptosis(P<0.01).However,Del-1 treatment did not alleviate the effects of blocking SERCA2 on ER stress,inflammatory response,and neuronal cell apoptosis(P>0.05).In conclusion,this study proposed that Del-1 could reduce ER stress,inflammatory response,and nerve cell apoptosis in spinal cord injury by enhancing the expression of SERCA2.本文探索发育内皮细胞因子-1(Developmental endothelial locus-1,Del-1)对脊髓肌浆网内质网钙调蛋白2(sarcoplasmic reticulum Ca^(2+)ATPase 2,SERCA2)的影响,及其对脊髓损伤(spinal cord injury,SCI)的可能作用。48只小鼠随机均分为sham组、SCI组和SCI+CE组,每组随机均分为两个亚组,Del处理亚组给予尾静脉注射Del-1(1μg/d)连续1周,另一组注射等量生理盐水;实验1周后处死小鼠,取脊髓进行下一步处理。首先通过免疫印迹分析Del-1在脊髓中对SERCA2的作用;然后通过免疫印迹和荧光TUNEL分析Del-1对小鼠SCI内质网应激、炎症和凋亡的作用;最后通过免疫印迹和荧光TUNEL分析分析阻断SERCA2后Del-1对小鼠SCI内质网应激、炎症和凋亡的作用。结果表明Del-1处理增加了脊髓中SERCA2的表达(P<0.01),并且减弱了SCI诱导的ER应激、炎症和神经细胞凋亡(P<0.01);阻断SCI小鼠脊髓中SERCA2表达,促进ER应激、炎症反应和神经细胞凋亡(P<0.01),但Del-1处理并不能减少阻断SERCA2对ER应激、炎症反应和神经细胞凋亡的影响(P>0.05)。最终得出Del-1可以通过促进SERCA2表达降低脊髓损伤的ER应激、炎症反应和神经细胞凋亡。

关 键 词：SCI Del-1 SERCA2 INFLAMMATION Apoptosis 

分 类 号：R961[医药卫生—药理学]