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血清微小 RNA152-3p 在伴有进行性肾病的 2 型糖尿病中的过表达。

Overexpression of Serum Micro-RNA 152-3p in Type 2 Diabetes Mellitus with a Significant Elevation in Progressive Nephropathy.

机构信息

Department of Clinical & Chemical Pathology Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt.

Department of Internal Medicine, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt.

出版信息

Egypt J Immunol. 2020 Jun;27(2):81-92.

PMID:33548980
Abstract

Modulation of the immune inflammatory system has been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN); nevertheless, many of the underlying mechanisms are still unknown. A possible role of micro-RNA 152-3p in T2DM and DN has been suggested due to its immunomodulatory effect on the innate immunity. This case control study aimed, first, to determine the possible role of micro-RNA 152-3p in the pathogenesis of T2DM and DN by evaluating its serum expression in T2DM and DN patients. Second, to assess the performance of serum micro-RNAs 16 and 24 as endogenous control in TaqMan assays of micro-RNA analysis by real time PCR in such disease. Quantification of the expression of micro-RNA 152-3p by qRT-PCR was performed using serum of 70 subjects enrolled in this study and grouped into 20 apparently healthy non-diabetic participants (control group), 15 patients with T2DM without nephropathy (DM group) and 35 diabetic patients with nephropathy (DN group). In diabetic patients with nephropathy (DN) (P<0.001), or without nephropathy (DM) (P 0.004), the expression of micro-RNA 152-3p demonstrated a significant elevation in comparison to the controls. Also, the level of micro-RNA 152-3p showed a positive correlation with HbA1c and the duration of diabetes mellitus. The severity of nephropathy as evaluated by markers of renal disease progression; estimated (e)GFR and albumin/creatinine ratio (ACR) revealed a significant correlation with the level of micro-RNA 152-3p. In the same context, serum level of micro-RNA 152-3p was elevated in diabetics with advanced stage of nephropathy (macroalbuminuria) versus the rest of diabetics (without albuminuria and with microalbuminuria). Two one sided T procedure provided a strong statistical support for equivalence of both micro-RNA s 16 and 24. In conclusion, such findings may indicate a pathologic role of micro-RNA 152-3p in Type 2 diabetes mellitus and in the progression of diabetic nephropathy.

摘要

调节免疫炎症系统已被认为与 2 型糖尿病(T2DM)和糖尿病肾病(DN)的发病机制有关;然而,许多潜在的机制仍不清楚。由于 microRNA 152-3p 对先天免疫具有免疫调节作用,因此它在 T2DM 和 DN 中的可能作用已被提出。本病例对照研究旨在通过评估 T2DM 和 DN 患者血清中 microRNA 152-3p 的表达,首先确定其在 T2DM 和 DN 发病机制中的可能作用。其次,评估血清 microRNAs 16 和 24 作为实时 PCR TaqMan 分析中 microRNA 分析内源性对照的性能。通过 qRT-PCR 对 70 名入组研究的受试者的血清进行 microRNA 152-3p 的表达定量,并将其分为 20 名明显健康的非糖尿病参与者(对照组)、15 名无肾病的 2 型糖尿病患者(DM 组)和 35 名有肾病的糖尿病患者(DN 组)。在有肾病的糖尿病患者(DN)(P<0.001)或无肾病的糖尿病患者(DM)(P<0.004)中,与对照组相比,microRNA 152-3p 的表达显著升高。此外,microRNA 152-3p 的水平与 HbA1c 和糖尿病的持续时间呈正相关。通过评估肾脏疾病进展的标志物(估计的[e]GFR 和白蛋白/肌酐比值[ACR])评估的肾病严重程度与 microRNA 152-3p 的水平呈显著相关性。在同样的情况下,处于肾病晚期(大量蛋白尿)的糖尿病患者的血清 microRNA 152-3p 水平高于其余糖尿病患者(无蛋白尿和微量白蛋白尿)。单边 T 检验为 microRNA s 16 和 24 的等效性提供了强有力的统计支持。总之,这些发现可能表明 microRNA 152-3p 在 2 型糖尿病和糖尿病肾病进展中具有病理作用。

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