他克莫司对糖尿病大鼠肾组织NF-κB调节的影响  

Effect of FK506 on NF-κB activation and modulation in the kidney of early diabetic rats

作　　者：程志群[1] 陈姗姗[1] 吴洁[1] 齐向明[1] 吴永贵[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》2013年第3期267-271,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81270813);教育部高等学校博士学科点专项科研基金(编号:20093420110003)

摘　　要：目的观察糖尿病大鼠肾组织NF-κB的变化,探讨他克莫司(FK506)肾脏保护作用的机制。方法采用腹腔内注射链脲佐菌素诱导大鼠糖尿病模型。随机均分为对照组(A组)、模型组(B组)、FK506 0.5 mg/kg.d给药组(C组)及FK506 1.0 mg/kg.d给药组(D组)。4周后观察大鼠肾重/体重(RKW)、24 h尿白蛋白排泄率(UAER)及肾组织病理形态改变。应用免疫组化法和Western blot法检测肾组织中NF-κB p65及NF-κB p-p65的表达。结果 C、D组大鼠UAER明显低于B组(P<0.05,P<0.01)。D组大鼠RKW明显低于B组(P<0.05)。C、D组容积较B组均明显降低(P<0.05),D组肾小管间质-损伤指数也明显低于B组(P<0.01)。免疫组化法结果显示B组大鼠肾组织NF-κB p-p65蛋白表达明显高于A组(P<0.01),而与B相比,C、D组肾组织NF-κB p-p65表达明显减少(P<0.01,P<0.01)。Western blot法结果显示B组肾组织NF-κB p65表达较A组增加5.33倍,C、D组肾组织NF-κB p65表达较B组分别下降26.32%与47.37%。B组肾组织NF-κB p-p65表达较A组增加7.57倍,C、D组肾组织NF-κB p-p65表达较B组分别下降56.67%和70.00%。结论 FK506能显著改善糖尿病大鼠早期肾脏损害,其分子机制可能与下调NF-κB表达有关。Objective To study the effect of FK506 on NF-κB activation and modulation in the kidney of early diabetic rats. Methods Diabeties was induced with streptozotocin in rats, and FKS06 （0.5 or 1.0 mg/kg ·d） was o- rally administered once a day for 4 weeks. Relative kidney weight （ RKW）, 24-hour urinary albumin excretion rate （UAER） were measured. Kidney pathology was observed by light microscopy. The expression of NF-κB p65, NF- κB p-p65 were detected by immunohistochemistry or Western blot. Results Elevated UAER in diabetic rats was markedly attenuated by FK506 treatment with 0. 5 and 1.0 mg/kg ·d （P 〈0.05, P 〈0. 01 ）. Increased RKW in diabetic rats was only significantly reduced by FK506 treatment with 1.0 mg/kg ·d （P 〈 0.05 ）. Elevated glomer- ular volume was also significantly attenuated by FK506 administration with 0.5 and 1.0 mg/kg ·d （ P 〈 0.05 ）, and increased tubulointerstitial injury indices were only ameliorated by FKS06 treatment with 1.0 mg/kg ·d （P 〈 0. 01 ）. Immunohistochemistry showed that elevated NF-κB p-p65 expression in diabetic rates was significantly at- tenuated by FK506 treatment with 0. 5 and 1.0 mg/kg ·d （ P 〈 0. O1 ）. Western blot analysis demonstrated that the expression of NF-κB p65 and NF-t^B p-p65 in the kidney of diabetic rats were increased by 5.35 and 7.57 folds re- spectively as compared to control. FK506 treatment with 0.5 and 1.0 mg,/kg ·d could reduce the increased expres- sion of NF-κB p65 by 26.32% and 47.37%, and could reduce the increased expression of NF-κB p-p65 by 56.67% and 70.00%. Conclusion FK506 could ameliorate renal structural and functional injury in early experi- mental diabetic rats, the mechanism of which may be partly correlated with suppression of NF-κB in renal tissue. Key words diabetic nephropathy; FKS06 ; NF-κB

关 键 词：糖尿病肾病 FK506 NF-ΚB 

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