骨髓单个核细胞移植对大鼠脑梗死后影响的初步研究

Effect of bone marrow mononuclear cells transplantation in rats following ischemic stroke

目的研究骨髓单个核细胞(BMMNC)移植对大鼠脑梗死后损伤的保护作用以及相关机制。方法雄性SD大鼠96只随机分为假手术组、模型组、环氧化酶2(COX-2)抑制剂组(NS398 20mg/kg)和BMMNC组(1×10~7个BMMNC),每组24只。采用改良线栓法制备大脑中动脉永久闭塞模型,分别于模型成功后24、72h和7d取材观察,每个时间点8只。采用Zea-Longa法进行神经功能评分;TTC染色法测脑梗死体积;免疫组织化学染色和Western blot技术检测COX-2、白细胞介素1β(IL-1β)表达。结果 BMMNC组24、72h和7d时脑梗死体积明显低于模型组(P<0.05);COX-2蛋白表达[(0.133±0.032)vs(0.342±0.042)、(0.141±0.035)vs(0.362±0.062)、(0.150±0.032)vs(0.330±0.050),P<0.05]和IL-1β蛋白表达[(0.213±0.045)vs(0.272±0.055)、(0.231±0.087)vs(0.331±0.105)、(0.134±0.030)vs(0.163±0.053),P<0.05]水平明显低于模型组,BMMNC组与COX-2抑制剂组上述指标无显著差异(P>0.05)。结论 BMMNC移植可通过抑制脑内免疫炎性反应,显著改善脑梗死大鼠的神经功能,可能与下调COX-2、IL-1β表达有关。

Objective To study the protective effect of bone marrow mononuclear cells （BMMNC） transplantation in rats following ischemic stroke and its mechanism. Methods Ninety-six SD rats were randomly divided into sham operation group, model group, COX-2 inhibitor group and BMMNC group. Tissue samples were taken at 24 and 72 h and on day 7 after a model of middle cerebral artery occlusion （MCAO） was established by Longa occlusion. The neurological function of rats was scored according to the Zea Longa method. The ischemic stroke size was measured with TTC staining,and expressions of COX-2 and IL-1β were detected by Western blot and immunohistochemical staining. Results The ischemic stroke size was significantly smaller while the expression levels of COX-2 and IL-113 were significantly lower in BMMNC group than in model group at 24 and 72 h and on day 7 after the model was established （0. 133 ± 0. 032 vs 0. 342 ± 0. 042,0. 141±0. 035 vs 0. 362±0. 062,0. 150±0. 032 vs 0. 330±0. 050, P〈0. 05 ; 0. 213±0. 045 vs 0. 272±0. 055,0. 231±0. 087 vs 0. 331±0. 105,0. 134±0. 030 vs 0. 163±0. 053,P〈0.05）. No significant difference was found in ischemic stroke size and expression levels of COX-2 and IL-1β between BMMNC group and model group （P〉0.05）. Conclusion BMMNC transplantation can significantly improve the neurological function of rats following ischemic stroke by inhibiting the immune inflammatory reaction and downregulating the expression levels of COX-2 and IL-1β.