背景:经鼻腔黏膜给药是一种可以克服血脑屏障、减少外周不良反应、效能高的脑内给药方式.目的:验证经鼻腔长期输送骨髓基质细胞治疗大鼠缺血再灌注性脑损伤的可行性.方法:贴壁培养法分离大鼠骨髓基质细胞.缺血再灌注脑损伤大鼠随机分成实验组和对照组.实验组经鼻腔滴入骨髓基质细胞,对照组同法给予磷酸盐缓冲液,隔天1次,共4周.每周进行1次行为学评价,最后1次行为学评价后进行脑病理学检测.结果与结论:与对照组比较,从第2周开始神经病学严重程度评分和Morris水迷宫实验检测结果表明实验组行为学逐步改善(P < 0.05,P < 0.01).与行为学改善相一致,缺血再灌注导致对照组CA1区海马细胞数量减少了66%,而实验组CA1区细胞丢失明显要少,只丢失了25% (P < 0.01).说明了经鼻腔长期输注骨髓基质细胞具有改善大鼠缺血再灌注脑损伤的作用.%BACKGROUND: Nasal delivery is a highly effective way to deliver drug into the brain, which can overcome the blockage of blood-brain barrier and peripheral side-effects.rnOBJECTIVE: To explore the feasibility of long term intranasal delivery of bone marrow stromal cells for treatment of brain injury caused by ischemia reperfusion.rnMETHODS: Bone marrow stromal cells were sorted from rat whole bone marrow by adherent culture. Brain ischemia reperfusion rats were randomly divided into experimental group or control group. Bone marrow stromal cells or phosphate buffer saline were dropped into the nasal cavity of experimental group and control group respectively, once every 2 days for a total of 4 weeks. Rat behaviors were assessed once a week. Brain pathological examination was performed after the last behavior assessment.rnRESULTS AND CONCLUSION: Compared with the control group, the results of modified neurological severity score and Morris water maze test showed that rat behaviors of experimental group were gradually improved at 2 weeks after treatment (P < 0.05, P < 0.01). It corresponded to behavior improvement, and ischemia reperfusion resulted in 66% cell loss in hippocampal CA1 region in the control group; however, in the experimental group, the cell loss in hippocampal CA1 region was significantly lower to 25% (P < 0.01). Our data indicated that long term intranasal delivery of bone marrow stromal cells can improve the brain injury caused by ischemia reperfusion.
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