肾组织内皮素受体A、B在老年糖尿病肾病发展中的作用研究
2017-08-12何华妮
何华妮
(海南省琼海市人民医院 肾内科,海南 琼海 571400)
肾组织内皮素受体A、B在老年糖尿病肾病发展中的作用研究
何华妮
(海南省琼海市人民医院 肾内科,海南 琼海 571400)
目的探讨肾组织中内皮素受体A、B(ETAR、ETBR)表达变化在老年糖尿病肾病发展中的作用。方法选取2015年1月-2016年6月该院收治的糖尿病肾病老年患者34例,根据糖尿病肾病病理分型分为:糖尿病肾病Ⅰ级(D1组10例),Ⅱ级(D2组12例),Ⅲ级(D3组12例);选取同期在该院行肾肿瘤切除术后远离肾肿瘤的正常组织为对照组(10例)。免疫组织化学检测ETAR、ETBR的表达量;免疫荧光双染法定位ETAR、ETBR在肾组织的分布部位。收集生化检测指标,计算肾小球硬化率,进行相关性分析。结果D3组尿蛋白水平高于D2和D1组,差异有统计学意义(P<0.05);D3组肾小球滤过率(GFR)和白蛋白(Alb)与D1组比较差异有统计学意义(P<0.05);D3组和D2组肾小球硬化率均高于D1组,差异有统计学意义(P<0.05)。糖尿病肾病各组ETAR、ETBR表达量均高于对照组,差异有统计学意义(P<0.05);对照组ETAR表达量少于ETBR,随着病情加重糖尿病肾病患者肾组织中ETAR表达量逐渐增加,组间比较差异有统计学意义(P<0.05);D2组ETBR表达量最高,与D1组和D3组比较差异无统计学意义(P>0.05);ETAR/ETBR在各组比较差异有统计学意义(P<0.05)。ETAR在肾小管近端和远端均存在表达,ETBR主要表达于肾小管近端。糖尿病肾病患者肾组织中ETAR表达量与病程、尿蛋白水平、肾小球硬化率(ROG)呈正相关;ETBR表达量与病程呈负相关;ETAR/ETBR比值与病程、尿蛋白水平及ROG呈正相关,与Alb、GFR呈负相关。结论老年糖尿病患者肾组织中ETAR、ETBR表达量增加,ETAR/ETBR值倒置与病情发展呈正相关。
糖尿病肾病;肾组织;内皮素受体;老年人
Abstract:ObjectiveTo investigate the endothelin receptor A,B (ETAR,ETBR)expression in renal tissue of the development in elder diabetic nephropathy.MethodsFrom January 2015 to June 2016,34 elderly patients with diabetic nephropathy in our hospital were divided into 3 groups according to pathological type:10 cases of group D1(12 cases),grade D2 group(12 cases),grade D3 group.Patients underwent renal tumor resection from renal tumors in our hospital as the control group (10 cases).The expressions of ETAR and ETBR were detected by immunohistochemistry.The location of ETAR and ETBR in renal tissue was detected by immunofluorescence double staining method.Biochemical detection indexes were collected to calculate the rate of glomerular sclerosis,and the correlation was analyzed.ResultsThe urine protein level of D3 group was significantly higher than that of D2 and D1 group,the difference was statistically significant (P<0.05).Glomerular filtration rate(GFR)and albumin(Alb)had significant difference between group D3 and D1(P<0.05).D3 group and D2 group glomerular sclerosis rate were significantly higher than that in D1 group,thedifference had statistical difference (P<0.05).The expression of ETAR and ETBR in diabetic nephropathy group were significantly higher than the control group,the difference was statistically significant(P<0.05).The expression of ETAR was less than ETBR in the control group,with the aggravation of increased expression of ETAR in renal tissue of diabetic nephropathy patients,the differences between groups were statistically significant(P<0.05).The expression of ETBR in D2 group was the highest,and no statistically significant differences between D1 group and D3 group (P>0.05).ETAR/ETBR in each group had statistically significant difference(P<0.05).ETAR was expressed in proximal and distal renal proximal tubule.ETBR was mainly expressed in proximal tubule.The expression of ETAR in renal tissue of patients with diabetic nephropathy and duration,urinary protein level and ROG were positively correlated.The expression of ETBR was negatively related to the amount and duration.ETAR/ETBR ratio and the course of disease,urinary protein level,ROG were positively correlated,negatively correlated with Alb,GFR.ConclusionsThe expression of ETAR and ETBR in the renal tissues of the elderly patients with diabetes mellitus are significantly increased,and the inversion of ETAR/ETBR value is positively correlated with the development of the disease.
Keywords:diabetic nephropathy;renal tissue;endothelin receptor;elder
糖尿病肾病多发于老年人群,是导致糖尿病患者死亡的主要并发症之一[1]。研究发现,糖尿病肾病患者血浆和尿液中内皮素1(endothelin-1,ET-1)含量增加并参与了病情的发展,ET-1主要通过内皮素受体 A(endothelin type a receptor,ETAR)、内皮素受体 B(endothelin type b receptor,ETBR)2种受体亚型发挥作用[2-3]。相关研究[4]显示,正常人肾脏ETAR与ETBR的比值为1∶2,但糖尿病肾病患者肾组织ETAR和ETBR的变化仍处在动物实验层面,且结论存在争议[5-7]。本研究通过观察不同糖尿病肾病时期老年患者肾组织中ETAR和ETBR表达变化,探讨其与老年糖尿病发展的关系。
1 资料与方法
1.1 一般资料
选取2015年1月-2016年6月本院收治的糖尿病肾病老年患者34例。肾活检前均告知患者必要性和危险性,签署知情同意书;……
