METHODS: Four groups of 40 mature Sprague-Dawley male rats were allocated as follow; control, fasting, ADR, and ADR plus fasting. After 8 weeks of ADR administration urine, blood samples and kidneys were taken for assessment of serum creatinine (Cr), BUN, urinary proteins, indicators of oxidative damage (malondialdehyde (MDA), reduced glutathione (GSH) and Catalase (CAT) levels), histopathological examinations, immunohistochemical examinations for caspase-3, Sirt1, aquaporin2 (AQP2) and real time PCR for antioxidant genes; Nrf2, HO-1 in kidney tissues.
RESULTS: IF significantly improved serum creatinine, BUN and urinary protein excretion, oxidative stress (low MDA with high CAT and GSH), in addition to morphological damage to the renal tubules and glomeruli as well as caspase-3 production during apoptosis. Moreover, IF stimulates significantly the expression of Sirt1 and Nrf2/HO-1 and AQP2.
CONCLUSIONS: AQP2, Sirt1, Nrf2/HO-1 signaling may be upregulated and activated by IF, which alleviates ADR nephropathy. Enhancing endogenous antioxidants, reducing apoptosis and tubulointerstitial damage, and maintaining the glomerular membrane\'s integrity are other goals.
方法:将4组40只成年SD大鼠作为对照组,禁食,ADR,和ADR加上禁食。ADR给药8周后尿液,血液样本和肾脏用于评估血清肌酐(Cr),BUN,尿蛋白,氧化损伤指标(丙二醛(MDA),降低谷胱甘肽(GSH)和过氧化氢酶(CAT)水平),组织病理学检查,caspase-3,Sirt1,aquaporin2(AQP2)的免疫组织化学检查和抗氧化基因的实时PCR;肾组织中的Nrf2,HO-1。
结果:如果能显著改善血清肌酐,尿素氮和尿蛋白排泄,氧化应激(低MDA,高CAT和GSH),除了对肾小管和肾小球的形态学损伤以及凋亡期间caspase-3的产生。此外,IF显著刺激Sirt1和Nrf2/HO-1和AQP2的表达。
结论:AQP2、Sirt1、Nrf2/HO-1信号可能被IF上调和激活,减轻ADR肾病。增强内源性抗氧化剂,减少细胞凋亡和肾小管间质损伤,和保持肾小球膜的完整性是其他目标。