目的研究人胎盘底蜕膜间充质干细胞(hPDB-MSCs)抗炎特性对帕金森病(PD)模型大鼠多巴胺能神经元的影响。方法体外培养hPDB-MSCs,6.羟基多巴(6-OHDA)制备大鼠PD模型并按照随机数字表法分为模型组与移植组,每组32只。hPDB-MSCs尾静脉移植观察各组大鼠行为学改变。免疫组化检测移植后3d、1周、2周及4周各组大鼠损伤侧黑质酪氨酸羟化酶(TH)、离子钙接头蛋白(Ibal)表达。实时荧光定量PCR检测各时间点各组大鼠损伤侧黑质抗炎因子人白细胞介素-10(hIL-10)、人转化生长因子-β(hTGF-β)及肿瘤坏死因子-α(TNF-α)表达。结果hPDB-MSCs移植后1周、2周、4周,移植组大鼠阿朴吗啡诱导的平均旋转圈数明显低于模型组,差异有统计学意义(P〈0.05)。免疫组化结果显示移植组大鼠损伤侧黑质部位TH阳性细胞数较模型组明显增加,1周、2周、4周时差异有统计学意3Z(P〈0.05)。移植组大鼠损伤侧黑质部位Ibal阳性细胞则明显减少,4周时最为显著。mRNA水平,移植组大鼠hIL-10及hTGF-β表达均较模型组增加,而TNF-α表达量则逐渐降低。结论hPDB-MSCs尾静脉移植后能够通过抗炎机制抑制PD模型大鼠多巴胺能神绎元丧失,改善PD模型大鼠症状。
Objective To investigate whether human placental decidua basalis-derived mesenchymal stem cells (hPDB-MSCs) by tail vein infusion can inhibit the loss of dopaminergic neuron in rat models of Parkinson's disease (PD) via an anti-inflammatory mechanism. Methods The hPDB-MSCs were cultured in vitro; PD rat models were established by intracranial injection of 6-hydroxydopamine (6-OHDA), and then, they were divided into vehicle group and transplantation group; hPDB-MSCs were infused into the rats of transplantation group by tail vein. Behavior changes of each group were evaluated by apomorphine (APO)-induced rotational test. Substantia nigra (SN) of the injured side in each group 3 days and 1, 2 and 4 weeks after transplantation were stained with immunohistochemistry to observe the expression changes of tyrosine hydroxylase (TH) and ionized calcium bindingadaptor molecule-1 (Ibal). The expressions of human interleukin-10 (hIL-10), human transforming growth factor-β (hTGF-β) and tumor necrosis factor-α (TNF-α)in the substantia nigra (SN) of the injured side in each group 3 days and 1, 2 and 4 weeks after transplantation were detected by real time PCR. Results The number of mean APO-induced rotational circle in the transplantation group at 1, 2 and 4 weeks after transplantation was significantly smaller than that in the vehicle group (P〈0.05).Significant increase of TH-positive cells in the lesioned side of SN 4 weeks after transplantation was noted as compared with that of SN 3 day after transplantation in the transplantation group (P〈0.05); significant increase of TH-positive cells in the lesioned side of SN was also noted between the two groups 2 and 4 weeks after transplantation (P〈0.05); the number of actived microglias in the lesioned side of SN decreased in the transplanted group 4 weeks after transplantation. The mRNA expression levels ofhlL-10 and hTGF-β in the transplantation group 1 and 2 weeks after the transplantation were significantly hi