hUCMSCs通过抑制星形胶质细胞活化引起的炎症因子表达改善Aβ损伤大鼠学习记忆能力

hUCMSCs improves the learning and memory ability of Aβinjury rats by inhibiting the expression of inflammatory factors induced by astrocyte activation

目的观察侧脑室注射人脐带间充质干细胞(human umbilical cord mesenchymal stem cells,hUCMSCs)对阿尔茨海默病样大鼠学习记忆能力的影响,并进一步探讨胶质细胞活化及炎症因子在hUCMSCs改善阿尔茨海默病样大鼠学习记忆能力中的作用。方法实验共分5组,分别为对照组、假手术组、溶剂对照组、Aβ损伤组、hUCMSCs保护组。双侧海马CA1区定位注射Aβ制备AD样学习记忆障碍大鼠模型;通过Morris水迷宫行为学测试检测大鼠学习记忆能力;采用酶联免疫吸附测定法分析海马组织中炎症因子表达情况;采用Western blot检测海马脑区星形胶质细胞及小胶质细胞标志物表达。结果与Aβ损伤组相比,hUCMSCs保护组大鼠逃避潜伏期显著降低(P<0.05),平台区穿越次数及平台所在象限停留时间百分比显著提高(P<0.05)。与Aβ损伤组相比,hUCMSCs保护组大鼠海马组织内炎症因子TNF-α及IL-1β蛋白表达量显著降低(P<0.05),星形胶质细胞标志物GFAP表达显著降低(P<0.05)。结论 hUCMSCs移植可改善Aβ损伤大鼠的空间学习记忆能力,其神经保护作用与抑制星形胶质细胞活化、进而减少炎症因子表达有关。

Objective To investigate the protective effect of human umbilical cord mesenchymal stem cells(hUCMSCs)against Aβinduced learning and memory impairment in rats,and to explore the mechanism of the protective effect of hUCMSCs.Methods Male SD rats weighting 210-230 g were divided randomly into five groups with ten in each:control group,sham group,vehicle-control group,Aβinjury group,and hUCMSCs treatment group.The Morris water maze behavioral task was employed to test the spatial learning and memory ability of the animals 1 week after hUCMSCs treatment.The expression of TNF-αand IL-1βin the hippocampus were investigated by enzyme linked immunesorbent assay after behavioral test.The expression of glial fibrillary acidic protein(GFAP)and lonized calcium binding adaptor molecule 1 were investigated by Western blot.Results Compared with Aβinjury group,hUCMSCs treatment decreased the escape latency and increased the platform crossings number andⅣtime ratio in the Morris water maze behavioral task(P<0.05).Compared with Aβinjury group,hUCMSCs treatment decreased the expression of TNF-α(P<0.05),IL-1β(P<0.05),and GFAP(P<0.05)in the hippocampus of rats.Conclusion hUCMSCs treatment reversed the behavioral impairment of Aβtreated rats.Its neuroprotective effect is related to the inhibition of astrocyte activation and then to reduce the expression of inflammatory factors.