FK506对糖尿病大鼠肾组织骨桥蛋白表达的影响  

Effect of FK506 on regulation of osteopontin expression and its relevant mechanism in diabetic rat

作　　者：苏静[1] 吴永贵[1] 齐向明[1] 梁超[1] 

机构地区：[1]安徽医科大学第一附属医院肾脏内科,合肥230022

出　　处：《安徽医科大学学报》2009年第1期31-35,共5页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金资助项目(编号:070413100)

摘　　要：目的探讨FK506对糖尿病大鼠肾小管-间质保护作用及可能的机制。方法应用链脲佐菌素腹腔一次性注射诱导大鼠糖尿病模型,随机分为对照组、模型组、FK506(0.5、1.0mg/kg)组。4周后观察大鼠肾重/体重与尿白蛋白排泄率(AER)的变化,并行肾小管-间质病理形态学分析。应用免疫组化和Western印迹方法检测骨桥蛋白(Os-teopontin,OPN)及NF-κBp65的表达。结果FK5061.0mg/kg给药组大鼠相对肾重明显低于模型组(P<0.05),FK5060.5与1.0mg/kg给药组大鼠AER水平明显低于模型组(P<0.05,0.01)。FK5061.0mg/kg给药组肾小管-间质损伤指数明显低于模型组(P<0.01)。免疫组化显示模型组肾小管-间质OPN表达阳性面积明显高于对照组(P<0.01),FK5060.5mg/kg与1.0mg/kg给药组肾小管OPN表达阳性面积明显低于模型组(P<0.01)。Western印迹显示模型组肾组织NF-κB蛋白表达较对照组增加6.19倍,FK5060.5与1.0mg/kg给药4周分别使肾组织OPN蛋白表达下降25.4%与47.4%。结论FK506对糖尿病肾小管-间质损伤有明显保护作用,其机制可能部分与抑制肾小管-间质的OPN有关。Objective To investigate protective effect of FK506 on the tubulointersititium and its possible mecha- nism in diabetic rat. Methods Diabetes was induced with streptozotoein in Sprague-Dawley rats, and FK506 （0.5 or 1.0 mg/kg） was orally administered once a day for 4 weeks. Relative kidney weight （RKW） and 24 hours uri- nary albumin excretion rate （AER） were measured. Tubulointersititium pathologic injury was observed by light microscopy. The expression of osteopontin（OPN） and nuclear factor-KB p65 （NF-κB p65 ） was determined by immunohistochemistry or Western blot analysis. Results Increased RKW was significantly reduced by FK506 treatment with 1.0 mg/kg（P 〈0. 05）, elevated AER was markedly attenuated by FK506 treatment with 0. 5 and 1.0 mg/kg （P 〈 0. 05, 0.01 ）. Increased indices for tubulointerstitial injury were only ameliorated by FK506 treatment with 1.0 mg/kg（ P 〈 0.01 ）. The expression of OPN protein and NF-KB p65 protein in kidney was significantly increased in diabetic rats while FK506 could significantly reduce the expression of OPN and NF-κB p65 protein. Conclusion FK506 could attenuate the injury of tubulointerstitium in diabetic rats, which may be at least partly correlated with suppression of increased OPN in renal tissue in diabetic rats.

关 键 词：糖尿病肾病/药物疗法 他罗利姆/治疗应用 唾液糖蛋白类 

分 类 号：R587.24[医药卫生—内分泌] R979.5[医药卫生—内科学]