糖尿病肾病患者肾组织Nsun2表达及意义

Expression and significance of Nsun2 in diabetic nephropathy

目的观察糖尿病肾病(DN)患者肾组织Nsun2表达变化,探讨其与临床病理特征的关系。方法2020年12月—2022年12月河南省人民医院诊治DN患者25例为DN组(DNⅠ~Ⅱ期10例,DNⅢ~Ⅳ期15例),肾癌患者20例为肾癌组,取DN组肾活检组织及肾癌组癌旁正常肾组织,采用PAS染色观察不同病理分期DN患者及肾癌组肾组织病理表现,采用免疫组织化学法检测肾组织Nsun2表达情况。比较2组体质量指数、高血压病史及基线血红蛋白、白蛋白、血肌酐、尿素、尿白蛋白/肌酐比值(UACR)、估算肾小球滤过率(eGFR)、C反应蛋白、凝血酶原时间、纤维蛋白原等实验室指标。采用Pearson和Spearman相关法分析DN患者肾组织Nsun2表达与实验室指标的相关性。结果DN组血肌酐[(81.00(66.00,137.50)μmol/L]、尿素[(6.59(5.50,9.04)mmol/L]、纤维蛋白原[(46.70±12.30)mg/L]水平及UACR[2803.00(1185.60,4948.00)mg/g]均高于肾癌组[70.00(58.25,77.75)μmol/L、5.86(4.29,6.30)mmol/L、(30.00±15.20)mg/L、19.89(10.92,29.31)mg/g](P<0.05),eGFR[83.31(47.50,95.54)mL/(min·1.73 m2)]、C反应蛋白水平[0.61(0.00,2.16)mg/L]均低于肾癌组[97.36(82.99,108.06)mL/(min·1.73 m2)、23.32(8.45,62.08)mg/L](Z=-2.238,P=0.025;Z=-4.496,P<0.001),体质量指数、高血压比率、凝血酶原时间及血红蛋白、白蛋白水平与肾癌组比较差异均无统计学意义(P>0.05)。DNⅠ~Ⅱ期肾组织可见肾小球肥大,基底膜增厚,系膜细胞增生,系膜基质增加,伴部分毛细血管袢受压、闭塞;DNⅢ期肾组织可见结节性肾小球硬化或K-W结节;DNⅣ期肾组织可见肾小球纤维化萎缩,肾小管纤维化,间质大量炎症细胞浸润。DN组肾组织肾小球足突广泛融合、基底膜弥漫性增厚,无电子致密物沉积。肾癌组癌旁正常肾组织肾小管上皮和肾小球细胞Nsun2呈强阳性表达,DNⅢ~Ⅳ期和DNⅠ~Ⅱ期肾组织Nsun2阳性表达均少于肾癌组癌旁正常肾组织,DNⅢ~Ⅳ期少于DNⅠ~Ⅱ期;DN组肾组织Nsun2表达(3.36±1.78)低于肾癌组癌旁正常肾组织(8.35±2.48)(t=7.865,P<0.001),DNⅢ~Ⅳ期(2.60±1.40)低于DNⅠ~Ⅱ期(4.50±1.71)(t=2.911,P=0.010)。DN患者肾组织Nsun2表达与eGFR呈正相关(r=0.553,P=0.004),与血肌酐、UACR均呈负相关(r=-0.556,P=0.004;r=-0.448,P=0.025)。结论DN患者肾组织Nsun2表达降低,DN病理分期越高、肾功能越差,Nsun2表达越低。

Objective To observe the change of Nsun2expression in renal tissues of patients with diabetic nephropathy(DN)and to explore its relationship with clinicopathological features.Methods From December 2020to December 2022in Henan Provincial People’s Hospital,25patients with DN(DN group,including 10cases of DN stageⅠtoⅡand 15cases of DN stageⅢtoⅣ),and 20patients with renal cancer(renal cancer group)were enrolled.The renal biopsy tissues of DN group and normal adjacent renal tissues of renal cancer group were taken and performed PAS staining to observe the pathological manifestations of the renal tissues of DN patients at different pathological stages and renal cancer group.The expression of Nsun2in renal tissues was detected by immunohistochemical method.The body mass index,hypertension history and baseline laboratory indexes[hemoglobin,albumin,blood creatinine,urea,urinary microalbumin/creatinine ratio(UACR),estimated glomerular filtration rate(eGFR),C-reactive protein,prothrombin time,fibrinogen]were compared between two groups.The correlation between Nsun2expression and laboratory indexes in renal tissues of DN group was analyzed by Pearson and Spearman correlation methods.Results The serum creatinine,urea,fibrinogen and UACR were higher in DN group[81.00(66.00,137.50)μmol/L,6.59(5.50,9.04)mmol/L,(46.70±12.30)mg/L,2803.00(1185.60,4948.00)mg/g]than those in renal cancer group[70.00(58.25,77.75)μmol/L,5.86(4.29,6.30)mmol/L,(30.00±15.20)mg/L,19.89(10.92,29.31)mg/g](P<0.05),the eGFR and C-reactive protein level were lower in DN group[83.31(47.50,95.54)mL/(min·1.73m~2),0.61(0.00,2.16)mg/L]than those in renal cancer group[97.36(82.99,108.06)mL/(min·1.73m~2),23.32(8.45,62.08)mg/L](Z=-2.238,P=0.025;Z=-4.496,P<0.001),and there were no significant differences in the body mass index,hypertension rate,prothrombin time,and levels of hemoglobin and albumin between two groups(P>0.05).Glomerular hypertrophy,basement membrane thickening,mesangial cell proliferation,mesangial matrix increase,and partial capillary loop compression and occlusion were observed in the renal tissues of DN stageⅠ-Ⅱ.Nodular glomerulosclerosis or K-W nodule was showed in the renal tissues of DN stageⅢ.Glomerular fibrosis and atrophy,renal tubule fibrosis,and interstitial infiltration of a large number of inflammatory cells were observed in the renal tissues of DN stageⅣ.DN patients were found extensive fusion of glomerular foot process,diffuse thickening of basement membrane,and no deposition of electron dense matter.The expression of Nsun2 was strongly positive in renal tubular epithelium and glomerular cells in normal adjacent renal tissues of renal cancer group.Nsun2positive expression was lower in the renal tissues of DN stageⅢ-Ⅳand DN stageⅠ-Ⅱthan that in the normal adjacent renal tissues of renal cancer group,and was lower in the renal tissues of DN stageⅢ-Ⅳthan that in the renal tissues of DN stageⅠ-Ⅱ.The expression of Nsun2was lower in the renal tissues of DN group(3.36±1.78)than that in the normal adjacent renal tissues of renal cancer group(8.35±2.48)(t=7.865,P<0.001),and was lower in the renal tissues of DN stageⅢ-Ⅳ(2.60±1.40)than that in the renal tissue of DN stageⅠ-Ⅱ(4.50±1.71)(t=2.911,P=0.010).The expression of Nsun2in the renal tissues of DN patients was positively correlated with eGFR(r=0.553,P=0.004),and negatively correlated with blood creatinine and UACR(r=-0.556,P=0.004;r=-0.448,P=0.025).Conclusions The expression of Nsun2reduces in the renal tissues of DN patients,and gets lower when the pathological stage of DN becomes higher and the renal function becomes worse.