大鼠缺血再灌注损伤脑内骨髓间充质干细胞移植抑制TNF-α表达的上调促进TGFβ1表达的上调  

Transplantation of bone marrow mesenchymal stem cells in the brain of rats with cerebral ischemia-reperfusion injury decreases expression of TNF-α and increases expression of TGFβ1

作　　者：郝磊[1] 刘磊[1] 董岸莺[2] 田洪[1] 张玉波[1] 周虎传[1] 宋川[1] 牟长河[1] Hao Lei;Liu Lei;Dong Anying;Tian Hong;Zhang Yubo;Zhou Huzhuan;Song Chuan;Mou Changhe(Center of cerebrovascular Disease, No.324 Hospital of PLA, Chongqing 400020, China;Department of heart, kidney and respiration, No. 273 Hospital of PLA, Korla, Xinjiang 841000, China)

机构地区：[1]解放军第324医院脑血管病中心,重庆400020 [2]解放军第273医院心肾呼吸科,库尔勒841000

出　　处：《中国组织化学与细胞化学杂志》2017年第4期327-335,共9页Chinese Journal of Histochemistry and Cytochemistry

基　　金：重庆市基础与前沿研究计划项目(CSTC 2014jcyj A10077)

摘　　要：目的探讨骨髓间充质干细胞(bone marrow derived mesenchymal stem cells,bMSCs)移植对大鼠缺血再灌注损伤脑肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、转化生长因子β1(transforming growth factorβ1,TGFβ1)表达的影响。方法首先分离、培养与鉴定大鼠bMSCs。72只大鼠随机分为假手术组、模型组、bMSCs移植组和移植对照组,每组18只。模型组、bMSCs移植组与移植对照组均复制大脑中动脉栓塞缺血/再灌注(middle cerebral artery occlusion infarction/reperfusion,MCAO I/R)脑卒中大鼠脑梗死模型。模型复制1d后,bMSCs移植组于右侧脑室移植bMSCs,移植对照组注射相同剂量的生理盐水。细胞移植后第1d、第3d和第7d,分别对各组动物进行神经功能缺损度评分法(neurological severity scores,NSS)评分。采用TTC法检测脑梗死体积,随后取梗死灶周围缺血半暗带脑组织及其余各组相应组织,采用Real-time PCR、Western blot与免疫荧光染色分别检测各组织TNF-α、TGFβ1 m RNA及其蛋白的表达变化。结果 bMSCs移植后第3 d和第7d,bMSCs移植组NSS明显低于移植对照组和模型组。bMSCs移植后7d,bMSCs移植组脑梗死体积明显低于模型组及移植对照组。bMSCs移植后第1d、第3d和第7d,模型组与移植对照组中TNF-α和TGFβ1的表达明显高于假手术组,BMSCs移植组的TNF-α表达增加不如模型组与移植对照组明显,而TGFβ1表达的增加显著高于模型组与移植对照组。结论 bMSCs移植可促进脑梗死大鼠神经功能恢复,减少脑梗死体积,其机制可能与其抑制促炎细胞因子TNF-α的表达增加和促进抗炎细胞因子TGFβ1的表达增加有关。Objective To investigate the effect of bone marrow derived mesenchymal stem cells(bMSCs)transplantation on theexpression of tumor necrosis factor-α(TNF-α)and transforming growth factorβ1(TGFβ1)in rats with cerebral ischemia-reperfusioninjury.Methods bMSCs were isolated from rat bone marrow,cultured and identified.Seventy two rats were randomized into shamoperation group,model group,bMSCs transplantation group and transplantation control group,with18rats in each group.Rats in themodel group,bMSCs transplantation group and transplantation control group were used for preparing middle cerebral artery occlusioninfarction/reperfusion(MCAO I/R)of cerebral infarction stroke rat model,and the remaining underwent the sham operation.1d aftermodeling,bMSCs were transplanted into the rat lateral ventricle in the bMSCs transplantation group,and rats in the control group weregiven the injection of the same amount of normal saline.1d,3d and7d after bMSCs transplantation,rat’s neurological function wasscored by neurological severity scores(NSS),and cerebral infarct volume was tested by TTC staining.The peripheral ischemic infarctpenumbra tissues and the corresponding tissues in other groups were removed in which the expression of TNFα,TGFβ1at both mRNA and protein levels were evaluated by Real-time PCR,Western blotting and immunofluorescence stain respectively.Results3d and7dafter transplantation of bMSCs,the NSS of bMSCs transplantation group was significantly lower than that of the transplantation controlgroup and the model group.7d after bMSCs transplantation,the infarct volume of bMSCs transplantation group was significantlylower than that of model group and transplantation control group.1d,3d and7d after the transplantation,the expression of TNFαandTGFβ1in model group and transplantation control group were significantly higher than that in the sham operation group,the increaseof TNFαexpression in bMSCs transplantation group was significantly lower than that in model group and transplantation control group,but the

关 键 词：骨髓间充质干细胞 脑缺血再灌注 肿瘤坏死因子α 转化生长因子β1 

分 类 号：R743.3[医药卫生—神经病学与精神病学]