BMSCs介导STAT3对脑出血大鼠海马组织eIF2α、Glu表达水平的影响  

BMSCs mediated STAT3 on the expression of hippocampal tissue in rats with intracerebral hemorrhage

作　　者：林兆信 陈海云 陈海恋 黄优[1] 高唯一 张洪源 张羽康 王景[1] Lin Zhaoxin;Chen Haiyun;Chen Hailian;Huang You;Gao Weiyi;Zhang Hongyuan;Zhang Yukang;Wang Jing(Department of Neurology,Sanya Central Hospital(Hainan Third People's Hospital),Hainan 572000,China)

机构地区：[1]三亚中心医院(海南省第三人民医院)神经内科,海南572000

出　　处：《脑与神经疾病杂志》2023年第3期170-174,共5页Journal of Brain and Nervous Diseases

摘　　要：目的探讨骨髓间充质干细胞(BMSCs)移植对脑出血(ICH)大鼠海马组织真核细胞翻译起始因子2α亚基(eIF2α)、谷氨酸(Glu)表达水平的影响及其机制。方法100只SD大鼠,随机选取10只分离BMSCs,剩余90只采用Ⅳ型胶原酶构建ICH模型。90只大鼠随机分为假手术组、ICH组和BMSCs移植组,每组30只。造模成功后24h,BMSCs移植组大鼠经尾静脉注入BMSCs,其余2组注入等体积0.9%氯化钠溶液。观察大鼠一般情况,评估神经功能,测定脑组织含水量。蛋白印迹测定海马组织内质网应激相关因子、eIF2α及JAK/STAT3通路蛋白水平,高效液相色谱法测定Glu浓度,TUNEL法分析细胞凋亡情况。结果ICH组大鼠神经功能缺损评分(NSS)和脑组织含水量显著大于假手术组,海马组织葡萄糖调节蛋白78(GRP78)蛋白相对表达量显著低于假手术组,CAAT增强子结合蛋白同源蛋白(CHOP)和Caspase-12蛋白相对表达量显著高于假手术组,海马组织eIF2α蛋白相对表达量和Glu水平显著高于假手术组,海马神经细胞凋亡率显著高于假手术组,海马组织JAK、p-JAK、STAT3和p-STAT3蛋白相对表达量显著低于假手术组(P<0.05);与ICH组比较,BMSCs移植组大鼠NSS评分和脑组织含水量显著降低,海马组织GRP78蛋白相对表达量显著增加,CHOP和Caspase-12蛋白相对表达量显著降低,eIF2α蛋白相对表达量和Glu水平显著降低,海马神经细胞凋亡率显著降低,海马组织JAK、p-JAK、STAT3和p-STAT3蛋白相对表达量显著增加(P<0.05)。结论BMSCs移植可通过JAK/STAT3通路降低ICH大鼠海马组织eIF2α和Glu表达,抑制神经细胞凋亡,减轻内质网应激,从而达到减轻脑损伤,改善神经功能作用。Objective To investigate the effect of bone marrow mesenchymal stem cells(BMSCs)transplantation on the expression of eukaryotic translation initiation factor 2α(eIF2α)and glutamate(Glu)in hippocampus of rats with intracerebral hemorrhage(ICH)and its mechanism.Methods Ten of 100 SD rats were randomly selected to isolate BMSCs,and the remaining 90 rats were used to establish ICH model with typeⅣcollagenase.Ninety rats were randomly divided into sham operation group,ICH group and BMSCs transplantation group with 30 rats in each group.24 hours after successful modeling,rats in BMSCs transplantation group were injected with BMSCs via tail vein,and the other two groups were injected with equal volume of 0.9%sodium chloride solution.The general condition of rats was observed,the neurological function was evaluated,and the water content of brain tissue was measured.Western blotting was used to detect the levels of Er stress-related factors,eIF2αand JAK/STAT3 pathway proteins in hippocampus.The concentration of Glu was determined by high performance liquid chromatography(HPLC).TUNEL was used to analyze apoptosis.Results The NSS and water content of brain tissue in ICH group were significantly higher than those in sham operation group.The relative expression of CRP78 protein in hippocampus was significantly lower than that in sham operation group.The relative expression of chopand caspase-12 protein in CAAT enhancer binding protein was significantly higher than that in sham operation group.The relative expression of JAK,p-jak,STAT3 and p-STAT3 protein in hippocampus was significantly lower than that in sham operation group(P<0.05);compared with cerebral hemorrhage group,the NSS score and brain water content in BMSCs transplantation group were significantly decreased,and the relative expression of GRP78 protein in hippocampus was significantly increased.The relative expressions of JAK,p-jak,STAT3 and p-STAT3 in hippocampus were significantly increased(P<0.05).Conclusion BMSCs transplantation can reduce the expression o

关 键 词：脑出血 BMSCS移植 真核细胞翻译起始因子2α亚基 谷氨酸 JAK/STAT3通路 内质网应激 

分 类 号：R743.34[医药卫生—神经病学与精神病学]