中华实验外科杂志
中華實驗外科雜誌
중화실험외과잡지
CHINESE JOURNAL OF EXPERIMENTAL SURGERY
2013年
7期
1481-1483
,共3页
魏增华%郝怀勇%贺敏敏%李永涛%李立新
魏增華%郝懷勇%賀敏敏%李永濤%李立新
위증화%학부용%하민민%리영도%리립신
脑缺血%再灌注损伤%Janus激酶信号转导及转录激活因子3信号通路%骨髓间充质干细胞移植
腦缺血%再灌註損傷%Janus激酶信號轉導及轉錄激活因子3信號通路%骨髓間充質榦細胞移植
뇌결혈%재관주손상%Janus격매신호전도급전록격활인자3신호통로%골수간충질간세포이식
Cerebral ischemia%Reperfusion injury%Janus kinase-signal transducer and activators of transcription 3 signaling pathway%Bone mesenchymal stem cell transplantation
目的 观察大鼠骨髓间充质干细胞(BMSCs)和Janus激酶信号转导及转录激活因子(JAK-STAT)信号通路抑制剂AG490联合移植对大鼠局灶性脑缺血/再灌注损伤的神经保护作用.方法 制备大鼠大脑中动脉栓塞(MCAO)模型.按照随机数字表达分为5组,分别设为sham组、1％二甲基亚砜(DMSO)组、AG490组、BMSCs+ 1％ DMSO移植组、BMSCs+ AG490移植组.移植治疗后24h,Western blot检测脑缺血再灌后磷酸化STAT3、肿瘤坏死因子(TNF)-α蛋白表达变化,原位末端转移酶标记(TUNEL)法检测大鼠脑缺血区细胞凋亡水平.移植治疗后分别于3、7、14d对每组大鼠进行神经缺陷症状评分,14d后处死大鼠,氯化三苯四唑(TTC)法染色后计算脑梗死体积,干湿重法称量脑含水量.结果 AG490可以明显抑制脑缺血再灌注后STAT3的磷酸化水平,并且降低脑梗死相关炎性分子TNF-α的表达.BMSCs+ AG490移植组中大鼠脑缺血区细胞凋亡、脑梗死体积[(12.31±6.24)％]及脑含水量[(77.55±0.53)％]较其他各组明显降低(P＜0.05),移植14 d后BMSCs+AG490移植治疗组中大鼠Bederson神经缺陷症状评分为(1.63±0.35)分,较其他各组改善明显(P＜0.05).结论 BMSCs联合AG490移植疗法对脑缺血再灌注损伤有明显协同神经保护作用.
目的 觀察大鼠骨髓間充質榦細胞(BMSCs)和Janus激酶信號轉導及轉錄激活因子(JAK-STAT)信號通路抑製劑AG490聯閤移植對大鼠跼竈性腦缺血/再灌註損傷的神經保護作用.方法 製備大鼠大腦中動脈栓塞(MCAO)模型.按照隨機數字錶達分為5組,分彆設為sham組、1％二甲基亞砜(DMSO)組、AG490組、BMSCs+ 1％ DMSO移植組、BMSCs+ AG490移植組.移植治療後24h,Western blot檢測腦缺血再灌後燐痠化STAT3、腫瘤壞死因子(TNF)-α蛋白錶達變化,原位末耑轉移酶標記(TUNEL)法檢測大鼠腦缺血區細胞凋亡水平.移植治療後分彆于3、7、14d對每組大鼠進行神經缺陷癥狀評分,14d後處死大鼠,氯化三苯四唑(TTC)法染色後計算腦梗死體積,榦濕重法稱量腦含水量.結果 AG490可以明顯抑製腦缺血再灌註後STAT3的燐痠化水平,併且降低腦梗死相關炎性分子TNF-α的錶達.BMSCs+ AG490移植組中大鼠腦缺血區細胞凋亡、腦梗死體積[(12.31±6.24)％]及腦含水量[(77.55±0.53)％]較其他各組明顯降低(P＜0.05),移植14 d後BMSCs+AG490移植治療組中大鼠Bederson神經缺陷癥狀評分為(1.63±0.35)分,較其他各組改善明顯(P＜0.05).結論 BMSCs聯閤AG490移植療法對腦缺血再灌註損傷有明顯協同神經保護作用.
목적 관찰대서골수간충질간세포(BMSCs)화Janus격매신호전도급전록격활인자(JAK-STAT)신호통로억제제AG490연합이식대대서국조성뇌결혈/재관주손상적신경보호작용.방법 제비대서대뇌중동맥전새(MCAO)모형.안조수궤수자표체분위5조,분별설위sham조、1％이갑기아풍(DMSO)조、AG490조、BMSCs+ 1％ DMSO이식조、BMSCs+ AG490이식조.이식치료후24h,Western blot검측뇌결혈재관후린산화STAT3、종류배사인자(TNF)-α단백표체변화,원위말단전이매표기(TUNEL)법검측대서뇌결혈구세포조망수평.이식치료후분별우3、7、14d대매조대서진행신경결함증상평분,14d후처사대서,록화삼분사서(TTC)법염색후계산뇌경사체적,간습중법칭량뇌함수량.결과 AG490가이명현억제뇌결혈재관주후STAT3적린산화수평,병차강저뇌경사상관염성분자TNF-α적표체.BMSCs+ AG490이식조중대서뇌결혈구세포조망、뇌경사체적[(12.31±6.24)％]급뇌함수량[(77.55±0.53)％]교기타각조명현강저(P＜0.05),이식14 d후BMSCs+AG490이식치료조중대서Bederson신경결함증상평분위(1.63±0.35)분,교기타각조개선명현(P＜0.05).결론 BMSCs연합AG490이식요법대뇌결혈재관주손상유명현협동신경보호작용.
Objective To investigate the neuroprotective effect of combined application of rat bone mesenchymal stem cells (BMSCs) and janus kinase-signal transducer and activators of transcription 3 (JAK-STAT) signaling pathway inhibitor (AG490) on rat focal cerebral ischemia.Methods In all rats,the middle cerebral artery occlusion (MCAO) was produced by occlusion of right internal carotid artery with a nylon monofilament.100 male Sprague-Dawley (SD) rats were divided into four groups according to random digits table (n =20 in each group),including sham group,1％ DMSO transplanted group,AG490 transplanted group,BMSCs + 1％ DMSO transplanted group and BMSCs + AG490 transplanted group.The phosphorylated signal transducer and activator of transcription3 (STAT3) (Tyr705) protein was measured by using Western blotting 24 h after transplantation.Cell apoptosis was examined by TdT-mediated dUTP nick end labeling (TUNEL).The neurological defective scores were assessed at 3rd,7th,and 14th day after reperfusion respectively in each experiment and all the animals were then decapitated to determine the brain infarct volume and brain water content.Results The expression of phosphorylated (Tyr705) STAT3 was decreased significantly after right intracerebral ventricle injection.Co-transplantation of bone mesenchymal stem cells and AG490 could significantly decrease the number of apoptotic cells and infarct volume [(12.31 ±6.24) ％],brain water content in ischemia hemisphere [(77.55 ± 0.53) ％].The neurological defective scores in BMSCs ± AG490 transplanted group (1.63 ± 0.35) were lower than other transplanted groups (P ＜ 0.05).Conclusion Co-transplantation of bone mesenchymal stem cells and AG490 produces a synergistic neuroprotective effect.
