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目的:探究不同时间点移植后骨髓间充质干细胞(BMSCs)的选择性迁移对大鼠全脑缺血/再灌注模型认知功能的影响以及可能的分子机制。方法:成年雄性SD大鼠80只,随机分为四组,全脑缺血再灌注组(model组,n=20),假手术组(sham组,n=20),造模1 d后较早BMSCs移植组(early组,n=20),造模7 d后较晚移植组(late组,n=20)。结扎双侧颈总动脉并结合低血压建立大鼠全脑缺血/再灌注模型,后于不同时间点尾静脉移植GFP+BMSCs。造模后1、3、7、14 d用酶联免疫法(ELISA)检测模型损伤区域大鼠皮层和海马部位的SDF-1α和MCP-1的表达水平,28 d后进行Morris水迷宫检测认知改变,32 d通过免疫组织化学染色和Western blot观察GFP+BMSCs的分布情况。结果:水迷宫实验表明细胞移植组相比sham组参数有显著提升,且early组相比late组表现更好(P<0.05);GFP免疫组化和western结果表明,early组BMSCs移植后分布于海马更多(P<0.05),而late组中BMSCs在皮层分布更多(P<0.05);ELISA结果表明,造模后1 d模型大鼠海马区域的SDF-1α和MCP-1的表达水平呈现短暂的相对性上调(P<0.05),而造模7 d后相关皮层区域的SDF-1α表达缓慢上调(P<0.05)。结论:造模后早期(1 d)移植BMSCs比晚期能更好的改善模型大鼠的认知功能;造模后SDF-1α和MCP-1的时空变化可能介导了BMSCs的选择行迁移,后者直接决定了对模型大鼠的认知功能改善的疗效。
Objective: To investigate the effect of selective migration of bone marrow mesenchymal stem cells (BMSCs) on the cognitive function and possible molecular mechanisms after global cerebral ischemia / reperfusion in rats at different time points. Methods: Eighty adult male Sprague-Dawley rats were randomly divided into four groups: sham group (n = 20), sham operation group (n = 20) Early BMSCs transplantation group (early group, n = 20), late transplantation group 7 days after modeling (late group, n = 20). The model of global cerebral ischemia / reperfusion was established by ligating both common carotid arteries and hypotension. GFP + BMSCs were transplanted into caudal vein at different time points. The expression of SDF-1α and MCP-1 in the cortex and hippocampus were detected by enzyme-linked immunosorbent assay (ELISA) at 1, 3, 7 and 14 days after modeling. Morris water maze test On the 32nd day, the distribution of GFP + BMSCs was observed by immunohistochemistry and Western blot. Results: The water maze test showed that compared with the sham group, the parameters in the cell transplantation group were significantly increased (P <0.05), and the early and late groups showed that the early and late BMSCs were distributed in the The levels of BMSCs in the late group were more in the cortex (P <0.05). The results of ELISA showed that the expression of SDF-1α and MCP-1 in the hippocampus of the model rats at 1 d after modeling (P <0.05). However, the expression of SDF-1α in the relevant cortical regions was slowly up-regulated after 7 days of modeling (P <0.05). CONCLUSION: BMSCs transplanted in the early postburn stage (1 d) can better improve the cognitive function of the model rats than the late stage. The spatiotemporal changes of SDF-1α and MCP-1 after modeling may mediate the migration of selected BMSCs, The latter directly determines the improvement of cognitive function in model rats.