罗格列酮对IgA肾病小鼠肾小球核转录因子-κB和活化蛋白-1表达的影响

Effects of rosiglitazone on the expressions of renal glomerulus NF-κB and AP-1 in mice with IgA nephropathy

目的观察罗格列酮对IgA肾病小鼠肾组织核转录因子-κB(NF-κB)、活化蛋白-1(AP-1)表达的影响,探讨罗格列酮对IgA肾病的作用及其机制。方法昆明种小鼠30只,分为对照组、模型组、罗格列酮组,每组10只。模型组与罗格列酮组复制IgA肾病模型。第12周末收集尿液显微镜下行尿红细胞计数;摘眼球取血,检测血肌酐(Scr)、尿素氮(BUN);光镜下观察肾脏病理损害;免疫荧光法观察系膜区IgA沉积;免疫组化和Western blot法检测NF-κB和AP-I的表达。结果①模型组尿红细胞、血Scr、BUN较罗格列酮组明显增多(P<0.01);②模型组肾小球系膜细胞及基质增生、IgA沉积量较罗格列酮组明显增多(P<0.01);③模型组肾组织NF-κB,AP-1的表达较罗格列酮组与对照组均明显增高(P<0.01)。结论罗格列酮对IgA肾病小鼠肾脏起保护作用,其保护作用可能与下调NF-κB、AP-1的表达有关。

Objective To investigate the effects of rosiglitazone on the expressions of the nuclear factor-kappa B（NF-κB） and AP-1 in the renal tissues of experimental mice with immunoglobin A nephropathy（IgAN） and to explore the actions of rosiglitazone on IgAN and the possible underlying mechanism.Methods Thirty Kunming mice were randomly assigned into three groups（n=10 each）： the control group,model group and rosiglitazone group.The IgAN models were established in model group and rosiglitazone group by gavage of bovine serum albumin（BSA） together with injection of staphylococcus enterotoxin B（SEB） via the caudal vein.At the end of the 12th week,fresh urine was gathered for the quantitative test of hematuria.Blood was taken through the eye orbit after eyeball extirpation for the test of serun creatinine（SCr） and blood urea nitrogen（BUN）.Changes of mesangial cells and matrix in the kidney were observed by light microscopy.IgA deposition was measured by immunofluorescence staining in the glomerulus,and the expression of NF-κB and active proten-1（AP-1） in tubulointerstitial tissues were analyzed by immunohistochemistry and Western blot.Results ① The number of urinary erythrocytes,the level of BUN and the levels of SCr in the model group remarkably increased compared with those in rosiglitazone group（P0.01）.② There was marked proliferation of mesangial cells and matrix as well as an increase in IgA deposition in the model group as compared to the rosiglitazone group（P0.01）.③ The expressions of NF-κB and AP-1 in tubulointerstitial tissues in the model group remarkably increased as compared to those in the normal group and rosiglitazone group（P0.01）.Conclusion Rosiglitazon has protective effect on the kidneys in IgAN mice and the underlying mechanism may be correlated with the downregulation of the expressions of NF-κB and AP-1.