关键词: miR-27a, miR-27b, miR-29c, miR-200c, 转化生长因子-β1, 外泌体, 尿液, 糖尿病肾病

Abstract:

Objective To investigate the roles of urinary exosome miR-27a，miR-27b，miR-29c and miR-200c in the diagnosis of early diabetic nephropathy（DN）. Methods A total of 260 type 2 diabetes mellitus（T2DM）patients were enrolled from Jinhua People's Hospital from January 2021 to December 2022. According to urinary albumin excretion rate（UAER），T2DM patients were classified into simple T2DM group（135 cases），early DN group（82 cases） and clinical DN group（43 cases）. Another 50 healthy subjects from Jinhua People's Hospital were enrolled as control group. The general data of all the subjects were collected，and the expressions of urinary exosome miR-27a，miR-27b，miR-29c，miR-200c，urinary creatinine（UCr），urinary urea nitrogen（UUN），urinary transforming growth factor-beta 1（TGF-β1；corrected by UCr），glycated hemoglobin A1c（HbA1c），serum uric acid（UA）were determined. Pearson correlation analysis was used to evaluate the correlation between each index. Multiple stepwise regression analysis was used to evaluate the influencing factors for urinary TGF-β1. Receiver operating characteristic（ROC） curve was used to evaluate the efficacy of miR-27a，miR-27b，miR-29c and miR-200c in the diagnosis of early DN. Results The relative expression levels of urinary exosome miR-27a，miR-27b and miR-200c in healthy control group，simple T2DM group，early DN group and clinical DN group were increased successively（P<0.001），while the relative expression levels of miR-29c were decreased successively（P<0.001）. The levels of UUN，UCr，corrected TGF-β1，HbA1c and UA in simple T2DM group，early DN group and clinical DN group were higher than those in healthy control group（P<0.05）. The levels of UUN，UCr，UA，corrected TGF-β1 and UAER in simple T2DM group，early DN group and clinical DN group were increased successively（P<0.001）. Urinary exosome miR-27a，miR-27b and miR-200c were positively correlated with UCr and corrected TGF-β1（P<0.01），while miR-29c was negatively correlated with UCr and corrected TGF-β1（P<0.001），and there was no correlation with UUN and UA（P>0.05）. HbA1c，UCr and urinary exosome miR-27a，miR-27b，miR-29c and miR-200c were independent influencing factors for corrected TGF-β1（P<0.01）. The areas under curves（AUC） of urinary exosome miR-27a，miR-27b，miR-29c and miR-200c for the diagnosis of early DN by single determinations and combined determination were 0.823，0.855，0.799，0.557 and 0.923，respectively. Conclusions The combined determination of urinary exosome miR-27a，miR-27b，miR-29c and miR-200c has good diagnostic value for early DN.

Key words: MiR-27a, MiR-27b, MiR-29c, MiR-200c, Transforming growth factor-beta 1, Exosome, Urine, Diabetic nephropathy