Tacrolimus对糖尿病大鼠肾脏巨噬细胞Toll样受体2与4表达的影响  

Effect of tacrolimus on expression of Toll-like respectors 2 and 4 on macrophage in the kidney of early diabetic rats

作　　者：陈姗姗[1] 齐向明[1] 张炜[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,安徽合肥230022

出　　处：《中国药理学通报》2013年第3期377-381,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81270813);教育部高等学校博士学科点专项科研基金资助项目(No20093420110003)

摘　　要：目的探讨Toll样受体(Toll-like receptor,TLR)2和TLR4在糖尿病大鼠肾脏巨噬细胞的表达水平及tacrolimus对其的调节作用。方法将40只Wistar大鼠随机分为对照组、模型组、tacrolimus(0.5、1.0 mg.kg-1)给药组,通过腹腔注射链脲佐菌素(STZ)诱导糖尿病模型,4周后测大鼠血糖、相对肾质量、尿白蛋白排泄率(UAER),应用免疫组化单染及双染方法检测肾组织ED-1+细胞、NF-κB-p-p65+细胞及ED-1+TLR2+细胞、ED-1+TLR4+细胞的表达。结果 ta-crolimus 1.0 mg.kg-1给药组大鼠相对肾质量明显低于模型组(P<0.05),tacrolimus(0.5、1.0 mg.kg-1)给药组大鼠UAER较模型组明显减少(P<0.05或P<0.01)。免疫组化显示:模型组大鼠肾组织ED-1+、ED-1+TLR2+、ED-1+TLR4+及NF-κB-p-p65+细胞数明显高于对照组(P<0.01),tacrolimus 0.5与1.0 mg.kg-1给药组ED-1+细胞数与模型组比较无差异,而ED-1+TLR2+、ED-1+TLR4+及NF-κB-p-p65+细胞数则明显低于模型组(P<0.05)。结论糖尿病大鼠肾脏巨噬细胞TLR2和TLR4的过度表达与巨噬细胞的活化及由此引发的炎症反应有关,tacrolimus可通过直接或间接作用下调肾脏巨噬细胞TLR2与TLR4表达,从而抑制与TLR-NF-κB信号转导及调控途径有关的炎症反应。Aim To investigate the expression of Toll-like receptor（TLR）2 and TLR4 on macrophage in the kidney of early diabetic rats and the effect of tacrolimus on them.Methods Forty Wistar rats were divided into normal control,diabetes and tacrolimus treated groups.Diabetic rats were induced with streptozotocin,and tacrolimus（0.5 or 1.0 mg·kg-1） was orally administered once a day for 4 weeks.The blood glucose,relative kidney weight（RKW） and 24 hour urinary albumin excretion rate（UAER） were determined.ED-1＋,NF-κB-p-p65＋,ED-1＋TLR2＋ and ED-1＋TLR4＋ cells were measured with immunohistochemistry and double immunohistochemistry.Results Increased RKW was only significantly reduced by 1.0 mg·kg-1 tacro limus treatment（P0.05）.Elevated UAER was markedly attenuated by 0.5 and 1.0 mg·kg-1 tacrolimus treatment（P0.05,0.01）.There was a marked accumulation of ED-1＋ cells in diabetic kidney,which were not inhibited by 0.5 and 1.0 mg·kg-1 tacrolimus treatment.ED-1＋TLR2＋ cells,ED-1＋TLR4＋ cells and NF-κB-p-p65＋ cells were significantly elevated in the kidneys from diabetic group,while they were significantly inhibited by 0.5 and 1.0 mg·kg-1 tacrolimus treatment（P0.05）.Conclusions Increased TLR2 and TLR4 expression on macrophage in the kidney of early diabetic rats may be correlated with inflammatory response caused by macrophage activation.Tacrolimus may directly or indirectly downregulate TLR2 and TLR4 expression on macrophage and inhibit inflammatory response related to TLR-NF-κB signal transduction in the kidney.

关 键 词：糖尿病肾病 巨噬细胞 TACROLIMUS TOLL样受体2 TOLL样受体4 NF-ΚB 

分 类 号：R-332[医药卫生] R322.61