尿激酶联合黄芪对环孢素A大鼠慢性肾纤维化组织中核因子-κB表达的影响及意义

目的探讨尿激酶（uPA）联合黄芪（AM）对环孢素A（CsA）大鼠慢性肾纤维化组织中核因子-κB（NF-κB）表达的影响及意义。方法采用1：7服灌胃CsA（25mg·kg^-1·d^-1）制备大鼠慢性肾纤维化模型，将大鼠随机分为5组：对照组、模型组、uPA组、AM组及联合治疗组，4周末取标本。HE染色观察肾脏组织结构变化；采用试剂盒测定肾组织羟脯氨酸的含量；应用免疫荧光观察P-p65的表达及定位；采用Western印迹法检测大鼠肾组织P—065、p65、IκBα和IκBβ的蛋白表达水平。结果与对照组相比，模型组肾小管损伤程度加重，羟脯氨酸含量增加，肾组织中NF-κB活化显著增强，p65由细胞质转移至细胞核，P-p65表达显著上调，IκBα降解明显增加（P均〈0．05）。与模型组相比，各治疗组肾小管损伤程度减轻，羟脯氨酸含量减少，P-p65表达被显著抑制，IκBα降解减少（P均〈0．05），且联合组的治疗效果更显著。IκBβ的蛋白表达水平各组间差异无统计学意义（P〉0．05）。结论NF-κB信号通路介导了肾脏纤维化的发生发展，uPA与AM能减轻肾脏纤维化，这可能与其能抑制NF-κB通路激活有关。

Effect of Urokinase and Astragalus Mongholicus on Expression of Nuclear Factor Kappa B in Rats with Cyclosporin A-Induced Chronic Renal Fibrosis

Objective To investigate the effect of urokinase(uPA) and astragalus mongholicus (AM) on expression of nuclear Factor kappa B(NF-κB) in rats with cyclosporin A(CsA)-induced chronic renal fibrosis.Methods Chronic renal fibrosis models were established by oral CsA (25 mgokg~(-1)od~(-1)).The rats were divided randomly into groups control,model,uPA,AM and combined treatment.Samples were taken at the end of weeks 4.The changes of renal organizational structure were observed by HE staining,p-p65 expression and localization by immunofluorescence,kidney tissue hydroxyproline content determined by kits,and p-p65,IκBαand IκBβexpression by Western blot analysis.Results When compared with control group,renal tubular injury was aggratated,hydroxyproline content increased,kidney tissue NF-κB activation significantly enhanced,p65 transferred from cytoplasm to nucleus,p-p65 expression remarkably up-regulated and IκBα degradation increased in model group (P＜0.05).As compared with model group,renal tubular injury decreased,hydroxyproline content decreased,p-p65 expression was inhibited obviously,IκBα degradation decreased in treatment groups (P＜0.05).The treatment effectiveness of combined treatment group was more pronounced.There was not significant difference in IκBβ protein expression between each groups (P＞0.05).Conclusion NF-κB signal pathway mediates the occurrence and development of renal fibrosis.uPA and AM can reduce renal fibrosis,which may be related to its inhibiting NF-κB signal pathway activation.