骨髓间充质干细胞联合Janus激酶信号转导及转录激活因子通路抑制剂治疗大鼠脑缺血再灌注损伤  

Co-transplantation of bone mesenchymal stem cells combined with janus kinase-signal transducer and activators of transcription 3 signaling pathway inhibitor （AG490） for focal cerebral ischemia/ reperfusion injury in rats

作　　者：魏增华[1] 郝怀勇[1] 贺敏敏[1] 李永涛[1] 李立新[2] 

机构地区：[1]济宁医学院附属滕州市中心人民医院神经外科,山东滕州277500 [2]南京医科大学第一附属医院神经外科

出　　处：《中华实验外科杂志》2013年第7期1481-1483,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（30973092、81171147）;江苏省“兴卫工程”医学重点人才基金资助项目（RC2007062）

摘　　要：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，Westernblot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（Trc）法染色后计算脑梗死体积，干湿重法称量脑含水量。结果ACA90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．仅的表达。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14d后BMSCs＋AG490移植治疗组中大鼠Bederson神经缺陷症状评分为（1．63±n35）分，较其他各组改善明显（P〈0．05）。结论BMSCs联合ACA90移植疗法对脑缺血再灌注损伤有明显协同神经保护作用。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 mid- dle cerebral artery occlusion （MCAO） was produced by occlusion of right internal carotid artery with a nylon monofilament. 100 male Spragne-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 re- spectively in each experiment and all the animals were then decapitated to determine the brain infarct vol- ume 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.

关 键 词：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 

分 类 号：R74[医药卫生—神经病学与精神病学]