摘要
目的:研究肾康灵联合强的松治疗阿霉素肾病(adriamycin-induced nephropathy)大鼠的作用机制。方法:除正常对照组18只外,雄性SD大鼠48只经尾静脉一次性注射阿霉素5.5mg/kg建立大鼠阿霉素肾病模型。造模2周后将造模成功的大鼠随机分成模型组、强的松组、肾康灵组及肾康灵加强的松组,每组12只,分别予相应的药物灌胃治疗。于造模2周及治疗后1、2、3周收集尿液检测24h尿蛋白含量;从眼眶后静脉丛采血,酶联免疫吸附法检测血清肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)含量,硝酸还原酶法检测血清一氧化氮(nitric oxide,NO)含量;于造模2周和治疗3周后,取大鼠脾脏及肾脏,采用ActiveMotif的专利技术检测脾脏单个核细胞中核转录因子-κB(nuclear factor-kappa B,NF-κB)p65含量变化,并分析以上指标间的相关性;透射电子显微镜观察肾小球足突改变。结果:单独应用强的松或肾康灵治疗后,大鼠NF-κB p65、TNF-α、NO及24h尿蛋白含量较模型组降低(P<0.01),融合的足突仅有部分恢复正常。肾康灵加强的松联合治疗可显著降低模型大鼠单个核细胞的NF-κB p65含量(P<0.01)、血清NO水平(P<0.01)和24h尿蛋白的排出量(P<0.05),并使融合的足突大部分恢复正常。肾康灵和强的松对血清TNF-α含量的降低无交互作用。结论:肾康灵加强的松联合治疗能延缓和改善阿霉素引起的肾损害,其作用机制可能与抑制NF-κB的异常活化,减少血清TNF-α及NO等炎症性因子的产生有关。
Objective： To study the mechanism of Shenkangling （SKL）, a compound traditional Chinese herbal medicine, combined with prednisone in treating adriamycin-induced nephropathy in rats. Methods： Sixty-six SD male rats were randomly divided into normal control group, untreated group, prednisonegroup, SKL group and SKL plus prednisone group. Except the normal control group, rats were injected once via caudal vein with adriamycin （5. 5 mg/kg） to induce nephropathy. Then, the rats were administered with prednisone, SKL, prednisone plus SKL or distilled water for 3 weeks, respectively. After harvest, 24-hour urine protein excretion, tumor necrosis factor-α （TNF-α） and nitric oxide （NO） contents in serum, and content of nuclear transcription factor-kappa B （NF-κB） p65 in mononuclear cells were determined, and correlation analysis among these parameters was performed. The content of NF-κB p65 was assayed with the patented method of Active Motif; TNF-α was assayed with enzyme-linked immunosorbent assay, and the content of NO was assessed by the method of nitrate reductase. The change of foot process in renal glomerulus was observed under an electron microscope. Results： When the rats were administered with prednisone, SKL correspondingly, the contents of NF-κB p65, TNF-α and NO as well as 24-hour urine protein excretion were lower than those in the untreated group （ P 〈0.01）, and the fusion of foot process only recovered partially. Compared with other treated groups, the contents of NF-κB p65 and NO as well as 24-hour urine protein excretion were significantly decreased in SKL plus prednisone group （ P 〈0.01, P 〈0. 05）, and the fusion of foot process recovered mostly also. There was no interaction between SKL and prednisone in decreasing the content of TNF-α. Conclusion： Renal injury can be postponed and improved when treated with SKL puls prednisone; it may contribute to the depression of abnormal activation of NF-κB, and the inhibition of production of TNF-α and NO.
出处
《中西医结合学报》
CAS
2009年第7期661-666,共6页
Journal of Chinese Integrative Medicine
基金
福建省自然科学基金资助项目(No.C0740002,C0440015)
福建中医学院B类课题(No.XB2006011)
