目的：利用木香烃内酯（Costunolide）诱导骨髓间充质干细胞（bMSCs）向神经样细胞分化，并通过诱导后的bMSCs对脑缺血再灌注大鼠模型进行治疗，研究木香烃内酯的体内外神经保护的药理学相关机制。方法：利用木香烃内酯诱导bMSCs向神经样细胞分化。此外，采用线栓法制作大鼠右脑中动脉阻断（MiddleCerebral Artery Occlusion，MCAO）再灌注模型，实验动物随机分为假手术组、模型组、MSC组及木香烃内酯诱导MSC组（诱导组）（n = 10），根据分组在再灌注2 h后由尾静脉注射相应细胞悬液或等量PBS，术后对各组大鼠进行神经功能损伤评分，于7日后取脑，检测脑组织含水量、计算梗死体积并进行HE染色。结果：木香烃内酯可使bMSCs向神经样细胞分化，且最佳诱导条件为10 μM木香烃内酯孵育细胞24 h，诱导后的bMSCs中胶质纤维酸性蛋白（GFAP）、神经元特异性烯醇化酶（NSE）、巢蛋白（Nestin）的表达量均有上调；体内实验中，诱导组大鼠脑组织含水量及梗死体积均显著低于模型组和MSC组（P＜0.05），此外，组织病理检测结果说明，诱导后的bMSCs能够促进半暗带组织结构恢复，相对于其他治疗组具有更好的疗效。结论：木香烃内酯可诱导bMSCs向神经样细胞分化，且用诱导后的bMSCs能够显著性的降低脑缺血再灌注损伤。

Objective: The differentiation of bone marrow mesenchymal stem cells (bMSCs) into nerve-like cells was induced by costunolide, and the treatment of cerebral ischemia reperfusion rat model with induced bMSCs was carriedout to study the pharmacological mechanism of intracorporal and extracorporeal neuroprotection of costunolide. Methods:BMSCs were induced to differentiate into neuron-like cells by costunolide. The reperfusion model of Middle CerebralArtery Occlusion (MCAO) was established by Suture-occluded method. MCAO models were randomly divided into asham operation group, a model group, a MSC group and induced MSC group (n = 10). According to groups, thecorresponding cell suspension or equivalent PBS were injected into the tail vein after 2 h reperfusion. The neuralbehavioral scores were measured after the models established. At 7 d after surgery, brain water content and the cerebralinfraction volume were measured and the HE- staining results were also analyzed. Results: Costunolide can inducebMSCs to differentiate into neuron-like cells, and the optimal induction condition was 10 μM costunolide incubatingcells for 24 h. The expression levels of NSE, GFAP and Nestin in bMSCs were upregulated after induction.In vivoexperiments, the water content and infarct volume of brain tissue in the induced group were significantly lower than thosein the model group and the MSC group (P < 0.05). In addition, the results of histopathological examination indicated thatthe bMSCs after induction could promote the recovery of tissue structure in the penumbra field, which had significantcurative effect compared with other treatment groups. Conclusion: Costunolide can induce the differentiation of MSCs intonerve-like cells. Treatment of cerebral ischemia with induced MSCs can significantly improve the efficacy.

国家自然科学基金委面上项目（81473337）：藏医抗脑缺血名方药效物质的神经保护机制研究，负责人：谭锐；四川中医药管理局四川省中医药产业发展专项资金项目（2016Z008）：中藏药大健康产品开发创新团队，负责人：谭睿；中国博士后科学基金会面上资助一等资助（2018M631098）：智能靶向胶束在脑缺血再灌注损伤治疗中的应用，负责人：谭立伟。