骨髓基质细胞及其上清液对缺氧缺血脑损伤大鼠海马齿状回突触素表达的影响及机制

摘要

Objective To analyze the expression of synaptophysin (SY) in hippocampal dentate gyrus of rats with hypoxic-ischemic brain damage(HIBD) after the injection of bone marrow stromal cells(BMSCs) and its supernatant into the lateral ventricle and to explore the mechanism of potential effects. Methods Eighty 7-day-old sprague-dawley(SD) rats were randomly divided into sham group, control group, cell group and supernatant group, with 20 rats in each group. The HIBD model was established via the ligation of left carotid arteries followed by 2-hour hypoxia. One week later, control group was injected with 0.01 mol/L PBS via the left ventricle. Meanwhile, cell and supernatant group were injected with BMSCs and supernatant harvested from BMSC culture, respectively, via the same route. For spam group, the left carotid arteries were separated but not ligated, and no hypoxia treatment was imposed on this group. They also received 0.01mol/L PBS injection one week post surgery. After 8 weeks, the expression of SY in the dentate gyrus of rats was measured. Results Compared with sham group, model group showed significantly lower IOD (integral optical density) of SY positive material in the dentate gyrus(P < 0.05). Compared with model group, supernatant group and cell group exhibited significantly increased IOD values (P < 0.05), but there was no significant difference between cell group and supernatant group (P > 0.05). Conclusions BMSCs and supernatant injected via the lateral cerebral ventricle can increase SY expression in the hippocampal dentate gyrus of HIBD rats and promote synapse formation. The mechanism of this effect may be related to cytokine secretion by BMSCs which promotes synapse formation.%目的：观察骨髓基质细胞（BMSCs）及其上清液对缺氧缺血脑损伤（HIBD）大鼠海马齿状回突触素（SY）表达的影响及其机制。方法：将80只7日龄SD 大鼠随机分成假手术组、模型组、细胞组和上清液组，各组20只。采用结扎左颈总动脉、术后持续缺氧2 h建立HIBD模型。模型组大鼠于造模术后1周经左侧脑室注入0．01 mol／L 的 PBS 溶液，细胞组和上清液组大鼠于术后1周分别以相同方法注入等体积的BMSCs和BMSCs培养基上清液；假手术组仅分离左颈总动脉，但不结扎，术后不进行缺氧干预，其余处理同模型组。于侧脑室注射术后8周，检测大鼠海马齿状回SY的表达水平。结果：模型组大鼠海马齿状回SY阳性物质累积吸光度（IOD）值较假手术组降低（P＜0．05），细胞组和上清液组其IOD值均较模型组增加（P＜0．05），而细胞组和上清液组其IOD值比较差异无统计学意义（P＞0．05）。结论：BMSCs及其上清液经侧脑室注入均能提高HIBD大鼠海马齿状回SY表达，促进突触生成；其主要机制可能与BMSCs分泌的细胞因子有关。