BMSCs移植治疗对PD模型大鼠脑纹状体内AADC表达的影响及其机制研究

Study on the effect and potential mechanism of BMSCs transplantation therapy on the AADC expression in the cerebral striatum of PD model rats

为了探讨骨髓间充质干细胞(BMSCs)移植治疗对PD模型大鼠脑纹状体内芳香族氨基酸脱羧酶(AADC)表达的影响及其可能机制,试验分别提取正常大鼠(N组)、PD模型大鼠(M组)和BMSCs移植治疗大鼠(T组)脑纹状体的总RNA、总蛋白和miRNA,采用RT-PCR和Western-blot方法检测移植治疗前后AADC的mRNA和蛋白表达以及靶向AADC 3'-UTR的miRNA的表达。结果表明:与N组正常大鼠相比,大鼠脑纹状体内AADC mRNA的表达在BMSCs移植治疗前后(M组和T组)均不存在显著差异,但是与mRNA表达不一致的是AADC蛋白表达在M组极显著下降(P<0.01),T组极显著回升(P<0.01)。靶向AADC的miR-3065-5p、miR-7a-1-3p、miR-31a-5p表达在M组极显著上升(P<0.01),但在T组表达极显著下降(P<0.01)。说明BMSCs移植治疗能够增加脑纹状体内AADC蛋白的表达,并且该过程可能受到下调miRNA的转录后调控。

To investigate the effect and the possible mechanism of bone marrow mesenchymal stem cells （BMSCs） transplantation therapy on the expression of aromatic amino acid decarboxylase （AADC） in the cerebral striatum of Parkinson＇s disease （PD） model rats, total RNA, total protein and miRNA were extracted from the cerebral striatum of normal rats as N group）, PD rats as M group and BMSCs transplanted rats as T group in the test, respectively. PCR and Western Blot methods were used to detect the expression of AADC mRNA, protein and miRNA tar- geting AADC 3 ^- UTR before and after transplantation therapy. The results showed that there were no significant differences in the AADC mR- NA expressions between M group and T group compared with the N group before and after BMSCs transplantation therapy. However, it is incon- sistent with the mRNA expression, AADC protein expression was highly significantly decreased（ P 〈 0.01 ）in the M group, while was significantly increased（P 〈0.01） in the T group. The expressions of miR - 3065 - 5p, miR - 7a - 1 - 3p, and miR - 31 a - 5p targeting AADC were highly significantly increased（ P 〈0. 01 ）in the M group, while were highly significantly decreased in the T group. The results indicate that B M-SCs transplantation therapy can increase the AADC protein expression in the cerebral striatum, and the process may regulated after the transcription of down - regulated miRNAs.