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目的研究糖尿病肾病(DN)患者肾组织miR-451a表达量与肾功能、肾纤维化的关系,探讨其临床应用价值。方法对DN患者进行肾活检,活检组织进行病理分级的同时提取RNA通过q PCR分析miR-451a、p15INK4b(p15)、E-caherin、α-SMA的表达变化;提取总蛋白分析各指标蛋白水平变化;并分析尿素、肌酐、尿酸、尿微量白蛋白/肌酐比(ACR)的改变。结果共收集DN患者46例,年龄39~64岁,男28例,女18例。病理分级为I级2例,Ⅱa级6例,Ⅱb级8例,Ⅲ级26例,IV级4例。DN组肾组织miR-451a表达量为对照组的0.2倍(P<0.05),p15的mRNA表达量为5.3倍(P<0.05)。随纤维化加重,miR-451a、E-caherin水平逐步下降,p15、α-SMA逐步升高(趋势分别为42.21、35.36、31.43、45.96,P<0.001)。miR-451a水平与p15、α-SMA、尿素、ACR呈负相关(r=-0.88,-0.83,-0.87,-0.86,P<0.05),与E-cadherin呈正相关(r=0.86,P<0.05)。P15的蛋白表达量(I级为对照组的2.62倍,Ⅱa级3.00倍,Ⅱb级3.76倍,Ⅲ级3.88倍,IV级4.58倍)、α-SMA的蛋白水平(升至2.24倍,2.82倍,3.00倍,3.10倍,3.64倍),而E-cadherin依次降至0.96,0.61,0.53,0.45,0.29。结论 DN肾纤维化过程中肾miR-451a呈低表达,与周期阻滞、EMT、肾功能存在相关性,可能成为纤维化新的评价指标及治疗靶标。
Objective To investigate the relationship between the expression of miR-451a and renal function and renal fibrosis in diabetic nephropathy (DN) patients and to explore its clinical value. Methods The expression of miR-451a, p15INK4b (p15), E-caherin and α-SMA in renal biopsies and biopsies of DN patients were detected by q-PCR. The total protein was analyzed for the changes of protein levels ; And analysis of urea, creatinine, uric acid, urine microalbumin / creatinine ratio (ACR) changes. Results A total of 46 patients with DN were collected, aged 39-64 years, 28 males and 18 females. The pathological grade was Grade I in 2 cases, Grade IIa in 6, Grade IIb in 8, Grade III in 26, and Grade IV in 4. The expression of miR-451a in DN group was 0.2 times that of the control group (P <0.05), and that of p15 mRNA was 5.3 times (P <0.05). With the aggravation of fibrosis, the levels of miR-451a and E-caherin gradually decreased and the levels of p15 and α-SMA gradually increased (trends were 42.21,35.36,31.43,45.96, P <0.001). The level of miR-451a was negatively correlated with p15, α-SMA, urea and ACR (r = -0.88, -0.83, -0.87, -0.86, P < 0.05). P15 protein level (2.62 times for the control group, 3.00 times for the Ⅱa level, 3.76 times for the Ⅱb level, 3.88 times for the Ⅲ level, and 4.58 times for the IV level), the protein level of α-SMA (up to 2.24 times and 2.82 times , 3.00 times, 3.10 times, 3.64 times), while E-cadherin decreased to 0.96,0.61,0.53,0.45,0.29. Conclusions The expression of renal miR-451a is low in DN renal fibrosis, which is correlated with cycle arrest, EMT and renal function, and may be a new evaluation index and therapeutic target for fibrosis.