环磷酰胺对糖尿病肾病大鼠蛋白尿的影响及其作用机制  

Effect and Mechanism of Cyclophosphamide on Proteinuria in Diabetic Nephropathy Rats

作　　者：李燕[1] 余晓洋[1] 张文静[1] 吕佳 王志刚[1] 邵耀中[1] 孙吉平[1] 张亚莉[1] LI Yan;YANG Xiaoyang;ZHANG Wengjing(Nephrology Department,the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an,710061)

机构地区：[1]西安交通大学第一附属医院肾脏病医院肾脏内科,西安710061

出　　处：《中国中西医结合肾病杂志》2021年第8期673-676,I0003,I0004,共6页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：陕西省科技攻关项目(No.2009K01-83)。

摘　　要：目的:研究环磷酰胺(CTX)能否减轻2型糖尿病肾病大鼠蛋白尿及其作用机制。方法:采用高糖高脂饮食+腹腔注射链脲佐菌素(STZ)的方法成功建立2型糖尿病肾病(DKD)大鼠模型。将其分为DKD组和CTX组,CTX组药物干预4周后对大鼠肾脏组织进行常规病理染色及电镜观察以及生化指标、足细胞标志性蛋白和炎症指标检测。结果:(1)2型糖尿病肾病的大鼠模型成模率82.35%;(2)与对照组相比,DKD组大鼠尿蛋白持续增多,Podocin减少,Desmin增多,CTX组居中,三组对比P<0.01;(3)糖尿病肾病早期的大鼠即能观察到肾小管间质炎症及纤维化因子异常。DKD组及CTX组的TGF-β1、CTGF、MCP-1均高于对照组(DKD组P<0.01;CTX组P<0.05),DKD组最高,与CTX组相比P<0.05。结论:环磷酰胺能够降低2型糖尿病肾病大鼠的尿蛋白,延缓肾脏病进展,并推测这与其稳定足细胞支架蛋白Podocin,减少足细胞转分化有关。Objective:To investigate whether cyclophosphamide(CTX)can reduce proteinuria in type 2 diabetic nephropathy rats and its mechanism of action.Methods:The rat model of type 2 diabetic nephropathy(DKD)was successfully established by high-sugar high-fat diet+intraperitoneal injection of streptozotocin(STZ).It was divided into DKD group and CTX group.After 4 weeks of drug intervention in CTX group,routine pathological staining and electron microscopy observation and biochemical indicators,podocyte marker proteins and inflammation indicators were performed on rat kidney tissues.Results:(1)The rat model of type 2 diabetic nephropathy was 82.35%;(2)Compared with the control group,the urine protein in the DKD group continued to increase,Podocin decreased,and Desmin increased.The CTX group was centered.Group comparison P<0.01;(3)In the early stage of diabetic nephropathy rats,tubular interstitial inflammation and fibrotic factor abnormalities were observed.TGF-β1,CTGF and MCP-1 in DKD group and CTX group were higher than those in control group(P<0.01 in DKD group;P<0.05 in CTX group),the highest in DKD group,P<0.05 compared with CTX group.Conclusion:Cyclophosphamide can reduce the urinary protein of type 2 diabetic nephropathy rats and delay the progression of kidney disease,and it is speculated that this is related to its stability of podocyte scaffold protein Podocin and reduction of podocyte transdifferentiation.

关 键 词：糖尿病肾病 蛋白尿 DESMIN PODOCIN 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]