外周血单个核细胞miR-146 a在2型糖尿病周围神经病变发病机制中的作用

摘要

Objective To explore the possible role of miR-146a in the pathogenesis of diabetic peripheral neuropathy( DPN) by investigating the correlation of miR-146a level in the peripheral blood mononuclear cells (PBMCs)with tumor necrosis factor α(TNF-α), interleukin-6(IL-6), and C reactive protein(CRP). Methods The expression levels of miR-146a in the PBMCs were measured using realtime PCR in 81 patients and 34 healthy individuals. The correlation of miR-146a expression with clinical parameters was analyzed. Results Compared to those in the healthy individuals and patients without DPN, miR-146a level was significantly decreased in diabetic patients with DPN while TNF-α, CRP, IL-6, HbA1C, systolic blood pressure, and homeostasis model assessment of insulin resistance index(HOMA-IR) were significantly increased(all P<0.05). Duration of diabetes, blood uric acid, serum creatinine, and urinary albumin to creatinine ratio in diabetics with DPN were higher compared with diabetics without DPN(all P<0. 05). The expression level of miR-146a was negatively correlated with diabetes duration, HOMA-IR, HbA1C, TNF-α, and IL-6. Multiple linear regression showed that HOMA-IR, HbA1C, TNF-α, and IL-6 were independent factors of miR-146a. Conclusion miR-146a may be involved in the development of DPN through inflammation, glucose metabolism, and insulin resistance.%目的通过观察外周血单个核细胞( PBMCs)中miR-146a的表达水平与炎症因子肿瘤坏死因子α(TNF-α)、C反应蛋白(CRP)和白细胞介素6(IL-6)的关系,探讨miR-146在糖尿病周围神经病变( DPN)发生发展中的可能作用机制。方法应用实时荧光定量PCR检测2型糖尿病37例、2型糖尿病合并DPN 44例及健康对照组34名受试者PBMCs miR-146a的表达水平,并与TNF-α、CRP、IL-6等临床指标进行相关性分析。结果与健康对照组、2型糖尿病不伴有DPN组相比,2型糖尿病伴有DPN组miR-146a的表达水平明显降低,而TNF-α、CRP、IL-6、HbA1C、收缩压、稳态模型评估的胰岛素抵抗指数( HOMA-IR)明显升高(均P<0.05)；DPN组患者的糖尿病病程、血尿酸、血肌酐、尿微量白蛋白/肌酐比值明显高于2型糖尿病不伴有DPN组(均P<0.05)。 Pearson相关分析提示miR-146a的表达水平与病程、HOMA-IR、HbA1C、TNF-α、IL-6呈负相关。多元线性逐步回归结果显示HOMA-IR、HbA1C、TNF-α、IL-6为miR-146a的独立影响因素(均P<0.05)。结论 miR-146可能通过炎症反应、糖代谢、胰岛素抵抗参与了DPN的发生发展。