2型糖尿病和糖尿病肾病患者血清微小RNA-148b-3p的水平变化及意义

Change and clinical significance of microRNA-148b-3p level in the serum of patients with type 2 diabetes mellitus and diabetic nephropathy

目的分析2型糖尿病和糖尿病肾病患者血清微小RNA-148b-3p（miR-148b-3p）的水平变化及其与临床和病理指标的相关性。方法入组人群分为3组，（1）糖尿病肾病组：。肾活检病理诊断明确为糖尿病肾病的患者（n=25，男14例，女11例）；（2）2型糖尿病组：尿微量白蛋F1／尿肌酐正常的2型糖尿病患者（n=10，男4例，女6例）；（3）正常对照组：健康体检者（n=9，男3例，女6例）。临床指标包括性别、年龄、24h尿蛋白量、收缩压（SBP）、舒张压（DBP）、血肌酐（Scr）、尿素氮（Urea）、胱抑素C（Cys—C）、血白蛋白（ALB）、尿微量白蛋白（UMA）、三酰甘油（TG）、胆同醇（TC）、高密度脂蛋白胆固醇（HDL—C）、低密度脂蛋白胆固醇（LDL—C）、血尿酸（UA）、空腹血糖（FBG）、糖化血红蛋白（HbA1c）、尿微量白蛋白／尿肌酐（UACR）和利用CKD—EPI公式计算的估算肾小球滤过率（eGFR）。实时定量PCR法测定入组人群的血清miR-148b-3p水平，分析血清miR-148b-3p水平与人组人群临床参数的关系。结果糖尿病肾病组、2型糖尿病组血清miR-148b-3p水平分别是正常对照组的1．82倍和1．73倍（均P〈0．05）。血清miR-148b-3p水平与HDL—C（r=-0．374，P=0．013）、UMA（r=0．426，P=O．004）、FBG（r=0．330，P=0．046）及TG（r=0．423，P=0．005）有明显相关性。多元线性回归分析显示UMA与血清miR-148b-3p独立相关（β=0．338，P=0．044）。血清miR-148b-3p在诊断2型糖尿病及糖尿病肾病的受试者丁作特征曲线（ROC）下面积分别为0．835和0．665。结论2型糖尿病和糖尿病肾病患者血清中miR．148b-3p水平显著升高。UMA与血清miR-148b-3p水平独立相关。血清miR-148b-3p有望作为糖尿病肾病诊断的潜在生物标志物。

Objective To detect the serum microRNA- 148b- 3p level in patients with diabetes mellitus and diabetic nephropathy, and to analyze its correlation with clinical and pathological indexes. Methods The research crowd was divided into three groups （1） diabetic nephropathy group： biopsy with diabetic nephropathy （n=25, 14 males, 11 females）; （2） type 2 diabetes mellitus group： type 2 diabetes mellitus patients with normal urinry mieroalbumin/urinary creatinine value （n= 10, 4 males, 6 females）; （3） normal control group： healthy subjects （n=9, 3 males and 6 females）. Clinical indicators included gender, age, 24-hour urine protein, systolic blood pressure （SBP）, diastolic blood pressure （DBP）, serum ereatinine （Ser）, urea （Urea）, cystatin-C （Cys-C）, blood albumin （ALB）,urine microalbumin （UMA）, triacylglycerol （TG）, total cholesterol （TC）, high- density lipoprotein cholesterol （HDL-C）, low-density lipoprotein cholesterol （LDL-C）, serum uric acid （UA）, fasting blood glucose （FBG）, glycated hemoglobin （HbAlc）, urine microalbuminuria / urinary creatinine （UACR）, and estimated glomerular filtration rate （eGFR） calculated by CKD- EPI formula. Real- time quantitative PCR was applied to verify the expression of microRNA - 148b - 3p in serum samples of the research crowds. The relationships between microRNA-148b-3p level and clinical features was also analyzed. Results The levels of serum microRNA - 148b - 3p in diabetic nephropathy group and in type 2 diabetes mellitus group were 1.82 times and 1.73 times of that in normal control group （P 〈 0.05, respectively）. The level of serum microRNA - 148b - 3p was significantly correlated with HDL - C （r=-0.374, P=0.013）, UMA （r=0.426, P=0.004）, FBG （r=0.330, P=0.046） and TG （r=0.423, P=0.005）. Muhiple linear regression analysis showed that UMA level was independently associated with serum microRNA-148b-3p level （β=0.338, P=0.044）. The area under the receiver operating characteristic curve （ROC） of serum microRNA - 148b - 3p in diagnosing type 2 diabetes mellitus and diabetic nephropathy was 0.835 and 0.665, respectively. Conclusions The level of serum microRNA- 148b- 3p of patients with type 2 diabetes mellitus or diabetic nephropathy significantly increases. The level of UMA is independently associated with serum microRNA-148b-3p level. Serum microRNA-148b-3p is expected to be a potential biomarker for the diagnosis of diabetic uephropathy.