FK506对早期糖尿病肾病大鼠足细胞损伤的保护作用  

Protective effect of FK506 on glomerular podocyte in early diabetic nephropathy rats

作　　者：常相帝[1] 王杰[1] 李冰[1] 甄军晖[2] 姜虹[3] 胡昭[1] 

机构地区：[1]山东大学齐鲁医院肾内科,济南250012 [2]山东大学齐鲁医院病理科,济南250012 [3]山东大学齐鲁医院教育部和卫生部心血管重构与功能研究重点实验室,济南250012

出　　处：《山东大学学报（医学版）》2012年第6期20-25,共6页Journal of Shandong University:Health Sciences

基　　金：国家科技支撑计划(2007BAI04B10)

摘　　要：目的探讨FK506对早期糖尿病肾病大鼠肾小球足细胞损伤的保护作用。方法将38只正常雄性SD大鼠随机分为正常对照组(N组)8只、糖尿病肾病组(DN组)10只、FK506治疗组(F组)10只、洛汀新治疗组(L组)10只,其中DN组、F组、L组应用链脲佐菌素(STZ)60 mg/kg腹腔注射建立糖尿病大鼠模型。F组成模4周后给予FK506 1 mg/(kg.d)灌胃,L组成模4周后给予洛汀新10 mg/(kg.d)灌胃,DN组与N组4周后给予等量蒸馏水灌胃,每4周末监测各组大鼠血糖(BS)、体质量(BW)、24 h尿蛋白定量,药物干预8周后测定各组大鼠的血肌酐(SCr)、尿素氮(BUN)、肾质量/体质量(KW/BW),在光镜、电镜下观察肾脏病理组织学改变,应用West-ern blot印迹检测足细胞特异标记物Nephrin的蛋白表达。结果①与N组比较,DN组大鼠BS、SCr、BUN、KW/BW、24 h尿蛋白定量均明显上升(P<0.05);与DN组比较,F组和L组上述指标除BS外均明显降低(P<0.05),且F组和L组之间差异无统计学意义(P>0.05);②光镜下,肾组织病理学观察N组无明显异常,DN组可见明显的肾小球体积增大,肾小球系膜细胞增生,系膜区增宽,基底膜增厚;F组、L组较DN组病理改变明显减轻(P<0.05),且F组和L组之间病理改变无显著性差异(P>0.05);③电镜下,DN组肾小球基底膜显著增宽,足突排列紊乱,足突增宽、融合,F组、L组较DN组上述病变有所减轻(P<0.05);④Western blot结果显示,DN组肾组织Nephrin蛋白表达较N组下降60.1%(P<0.05),F组和L组可明显恢复肾组织Nephrin蛋白的表达(P<0.05)。结论 FK506可能部分通过恢复糖尿病大鼠肾组织Nephrin蛋白表达、维护足细胞结构和功能的完整而发挥减少尿蛋白、延缓DN进展的作用。Objective To investigate the protective effect of FK506 on glomerular podocyte injury in early diabetic ne- phropathy rats. Methods Thirty-eight normal male SD rats were randomly divided into the normal control group（ N, n =8） , the diabetic nephropathy group（DN, n = 10）, the FKS06 treatment group（F, n = 10） , and the lotensin treat- ment group（ L, n = 10）. The diabetes mellitus models were established by intra-peritoneal injection of streptozotocin at a dosage of 60mg/kg in groups DN, F and L. The rats in group F were intra-gastriced with FK506（1 mg/kg. d） after 4 weeks. The rats in group L were intra-gastriced with lotensin（ 10 mg/kg . d） after 4 weeks, and the rats in the other two groups（ group DN and group N） were treated with distilled water at the same dosage after 4 weeks. Blood glucose（ BS）, body weight（BW） and 24-hour urine protein were detected every 4 weeks. Serum creatinine（ SCr）, blood urea nitrogen（BUN） and kidney weight/body weight（KW/BW） were detected at the end of 8 weeks of the drug treatment. Pathological changes of nephridial tissue were observed under a light microscope and an electron microscope. Expression of Nephrin was detected using Western blot. Results （!）SCr, BUN, KW/BW and 24-hour urine protein in groups DN, were significantly higher（P 〈 0.05） compared with the group N. The above indicators except for BS in groups F and L were significantly lower compared with group DN（ P 〈 0.05 ）, and there was no significant difference between the two groups （ P 〉 0.05 ） ; ②There was no significant abnormal pathological changes of nephridial tissue in group N under the light microscope. There were significantly increased glomerular volume, proliferative mesangial cells, broaden me- sangial area and thicken basement membrane in group DN. The above histopathological changes of groups F and L were less compared with group DN（P 〈0.05）, and there was no significant pathological difference between groups F and L （P 〉 0.05�

关 键 词：糖尿病肾病 FK506 足细胞 链脲佐菌素 Nephrin蛋白 

分 类 号：R692[医药卫生—泌尿科学]