骨髓间充质干细胞移植治疗急性一氧化碳中毒迟发性脑病大鼠*☆

背景：国内多采用药物治疗和高压氧治疗一氧化碳中毒迟发性脑病，但存在疗程长，见效慢，花费高等问题。 目的：观察骨髓间充质干细胞移植治疗一氧化碳中毒迟发性脑病前后神经元及细胞凋亡的变化。 方法：将SD大鼠抽签随机分为假手术组、对照组与干细胞移植组。制作一氧化碳中毒迟发性脑病模型后，干细胞移植组在造模后第0，3，6，12，24，72小时及1周时脑内注射同种异体骨髓间充质干细胞，对照组不进行细胞移植；假手术组扎闭颈外动脉，用PBS代替细胞悬液。 结果与结论：造模后3，6，12，24 h干细胞移植组脑内神经元核心抗原表达明显高于对照组与假手术组(P < 0.01)，干细胞移植各组脑内神经元核心抗原表达无明显差异(P > 0.05)。造模后0，3，6 h干细胞移植组脑内细胞凋亡平均吸光度值明显低于对照组与假手术组及其他干细胞移植组(P < 0.05)，且移植后第1周明显低于第2，3，4周(P < 0.05)。提示在一氧化碳中毒迟发性脑病大鼠体内移植间充质干细胞可以增加成熟神经元数量，其机制与减少细胞凋亡有关；移植的最佳时机为发病后0~24 h之间，细胞移植后的积极作用在第1周最明显。关键词：一氧化碳中毒迟发性脑病；骨髓间充质干细胞；神经元；凋亡；干细胞移植 doi:10.3969/j.issn.1673-8225.2012.19.025

Bone marrow stem cells transplantation for treatment of delayed encephalopathy after acute carbon monoxide poisoning in rats

BACKGROUND: The therapy of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) in our country mainly depends on drug or hyperbaric oxygen. But the treatment has the characters of longer course, lower effect and higher cost. OBJECTIVE: To observe the changes of mature neurons and cell apoptosis before and after bone marrow mesenchymal stem cells (BMSCs) transplantation for treatment of DEACMP. METHODS: SD rats were randomly divided into three groups: sham operation group, control group and transplantation group. The rat model with DEACMP was established and intracerebral injection of allogeneic BMSCs was performed in the transplantation group at 0, 3, 5, 12, 24, 72 hours and 1 week after modeling, and cell transplantation was not performed in the control group. In the sham operation group, the external carotid artery was tied off and the PBS was injected instead of cell suspension.  RESULTS AND CONCLUSION: The expression of neuron-core protein (NeuN) in rat brain in the transplantation group at 3, 6,12 and 24 hours were significantly higher than that in the control group and sham operation group (P < 0.01). There was no significant difference in NeuN expression at 3, 6, 12 and 24 hours (P > 0.05). The average absorbance value of apoptosis in the transplantation group across 0-hour, 3-hour and 6-hour three time points was significantly lower than that in the sham operation group and other transplantation groups (P < 0.05). The average absorbance value of apoptosis in 1 week group was significantly lower than that in 2-week, 3-week and 4-week groups (P < 0.05). Transplantating BMSCs into the DEACMP rat models through the carotid artery could increase the quantity of mature neurons, and the underlying mechanism has relationship with apoptosis reduction. The best time for transplantation was between the 0 hour and the 24 hours after falling ill and the positive effect was significant at 1 week after transplantation.