氧化苦参碱对阿霉素大鼠慢性肾纤维化组织中核因子-κB表达的影响

Effects of oxymatrine on expression of nuclear factor kappa B in kidneys of rats with adriamycin-induced chronic renal fibrosis

目的探讨氧化苦参碱(OM)对大鼠慢性肾纤维化组织中核因子-κB(NF-κB)表达的影响。方法实验第1天、第21天尾静脉注射阿霉素(2mg/kg)建立慢性肾纤维化大鼠模型,分为模型组、苯那普利治疗组和OM治疗组。正常对照组给予等量生理盐水尾静脉注射。检测各组的24h尿蛋白含量、血生化及肾脏组织病理改变,并应用免疫组织化学法检测肾组织内NF-κB、抑制性κB(IκB)蛋白的表达,并进一步分析NF-κB与IκB蛋白的表达、肾脏病理改变及肾功能损害的关系。结果苯那普利治疗组、OM治疗组的肾脏病理改变、肾功能损害均轻于模型组,第2次注射后8周时组织内NF-κB蛋白的表达轻于模型组,而IκB蛋白的表达高于模型组,但两者之间差异无显著性。模型组大鼠肾组织中NF-κB与IκB成负相关,而与肾脏病理改变及肾功能损害成正相关。结论OM可能通过下调阿霉素大鼠肾组织中NF-κB的表达而抑制肾纤维化的发生,从而起到保护肾脏的作用。

Objective To investigate the effects of oxymatrine on the expression of nuclear factor kappa B （NF-κB） in the kidneys of rats with adriamycin-induced chronic renal fibrosis. Methods TotaUy 120 Wistar rats were randomly assigned to normal control group, renal fibrosis model group, bcnazcpril treatment group and oxymatrinc treatment group （n=30）. The rats in the normal control were injected with normal saline via the tail vein, and those in the other 3 groups with adriamycin （2 mg/kg） on the 7th day and 21st day of the experiment, respectively. Oxymatrine （100 mg/kg） or benazepril （6 mg/kg） was given by gastric pcrfusion after the second injection. Every 4 weeks after the second injection, 5 rats in each group were killed to evaluate the pathological changes and functional impairment of the kidney. Immunohistochemistry was used to detect the expression of NF-κB and inhibitory kappa B （IKB） in the kidney. The association of NF-κB expression with IKB expression, pathological changes and functional impairment were studied. Results Oxymau＇ine and bcnazepril ameliorated renal fibrosis and functional impairment. Immunohistochemical staining revealed increased NF-κB expression and decreased IKB expression in the model group in comparison with oxymatrine and benazepril treatment groups 8 weeks after the second injection, but no significant difference was noted between the latter two groups. NF-κB expression,in the kidneys of rats with adriamycin-induced chronic renal fibrosis showed an inverse correlation with IKB expression and positive correlation with pathological changes and functional impairment. Conclusion Oxymatrine may inhibit renal fibrosis by down-regulating NF-κB expression, which may play a key role in protection against renal fibrosis.