[关键词]
[摘要]
目的 研究血清胰岛素样生长因子-1(IGF-1)水平在2型糖尿病(T2D)、帕金森病(PD)及T2D伴发PD(T2D-PD)患者之间的差异并探讨其转录后调控机制。方法 收集T2D患者21例、PD患者20例、T2D-PD患者17例以及正常对照25例,应用ELISA法检测血清IGF-1蛋白含量;实时荧光定量PCR(qRT-PCR)技术检测血清相关microRNAs的表达水平;miRanda分析软件预测miR-206可能靶向IGF-1 mRNA表达的作用位点。结果 T2D-PD患者血清IGF-1水平较PD组下降,但差异不显著,与正常对照组比较差异不显著,而较T2D组显著升高(P<0.001);T2D-PD组血清miR-206相对含量显著低于T2D组(P<0.01),与正常对照组和PD组比较无显著性差异;miRanda软件预测miR-206可以靶向性结合IGF-1 mRNA的3'-非编码区(3'-UTR),mirSVR评分为-1.285,PhastCons评分为0.6561。结论 miR-206介导的IGF-1表达增加可能是糖尿病伴发PD重要的病理生理机制,提示血清IGF-1水平可能成为糖尿病伴发PD早期临床诊断的关键指标之一。
[Key word]
[Abstract]
Objective To investigate the difference of serum insulin-like growth factor -1 (IGF-1) levels among patients with type 2 diabetes mellitus (T2D), Parkinson's disease (PD) and type 2 diabetes mellitus with Parkinson's disease (T2D-PD), and to explore the potential mechanism. Methods Totally 21 patients with T2D, 20 patients with PD, T2D-PD in 17 cases and 25 cases of normal control were collected. Serum IGF-1 contents were detected by ELISA and microRNAs expression was measured by qRT-PCR. Moreover, miRanda software was used to predict possible microRNAs in post-transcriptional regulation of IGF-1 mRNA. Results The concentration of IGF-1 in T2D-PD group was significantly higher than that in T2D group (P < 0.001), and there was no significant difference compared with that in normal control or PD patients; The relative content of serum miR-206 in T2D-PD was significantly lower than that in group T2D (P < 0.01), and there was no significant difference compared with that in normal control or PD patients; miRanda software predicted that miR-206 could target the 3'-UTR of IGF-1 mRNA, mirSVR score was -1.285, and PhastCons evaluation was 0.6561. Conclusion miR-206-mediated increase of IGF-1 expression may play an important role in the pathophysiology of diabetes associated with PD, suggesting that serum IGF-1 levels may be one of the key indicators for clinical diagnosis of diabetes mellitus with PD in early stage.
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[基金项目]
南京医科大学科技发展基金面上项目(2013NJMU088);南京医科大学教育研究课题(YB2017032);大学生创新创业计划项目(201510312025Z)