curcumenol and Kidney-Failure--Chronic

The present work aimed to explore the protective effects of curcumenol and evaluate its pharmacological mechanisms in 5/6 nephrectomy-induced chronic renal failure (CRF). Rats with CRF were administrated curcumenol and the effects on renal functions were investigated. Renal function examinations were carried out, whereas serum levels of inflammatory mediators, including NF-κB, MCP-1 and IL-1β were analyzed by ELISA. The mRNA expression levels of SIRT1, p65 and IκBα were measured by qRT-PCR, and the SIRT1 protein levels were analyzed by western blot and immunohistochemistry. Our results indicated that curcumenol significantly improved the renal functions in the CRF rats. Compared to the sham group, serum levels of NF-κB, MCP-1, IL-1β, and the mRNA expression levels of p65 were significantly increased (p < 0.01), whereas the mRNA expression level of IκBα was significantly decreased (p < 0.01) and the SIRT1 levels were dramatically down-regulated (p < 0.05) in the CRF groups. Treatment with curcumenol remarkably inhibited inflammatory responses as reflected by the reduced levels of inflammatory mediators (p < 0.01) and SIRT1 up-regulation (p < 0.05). Our findings suggested that curcumenol could improve the renal function in 5/6 nephrectomy-induced CRF rats, and the mechanisms might involve suppressing the associated inflammation and modulating the SIRT1 and NF-κB signaling pathways.. 本研究旨在评价莪术烯醇对5/6肾切除术诱导的慢性肾功能衰竭(CRF)的保护作用，并探讨其药理机制。研究给予5/6肾切除大鼠莪术烯醇治疗并评估莪术烯醇对肾功能的干预效果。ELISA检测血清中NF-κB, MCP-1和IL-1β等炎症因子的表达水平， qRT-PCR检测SIRT1, p65 和 IκBα的mRNA表达水平, western blot和免疫组化检测SIRT1 蛋白表达水平。结果表明莪术烯醇对CRF大鼠肾功能异常有明显改善作用。与假手术组比较, CRF组大鼠血清NF-κB, MCP-1和IL-1β水平及p65基因转录水平显著升高 (p < 0.01)， IκBα基因转录水平(p < 0.01) 及SIRT1表达水平显著降低 (p < 0.05)。莪术烯醇能够显著抑制炎症反应，表现为炎症相关分子水平的降低 (p < 0.01) 和SIRT1表达的上调 (p < 0.05)。初步研究表明莪术烯醇可改善5/6肾切除术后CRF大鼠的肾功能，其机制可能与抑制炎症反应、调控SIRT1/NF-κB信号通路有关。.

Topics: Animals; Kidney; Kidney Failure, Chronic; Nephrectomy; NF-kappa B; NF-KappaB Inhibitor alpha; Rats; RNA, Messenger; Sirtuin 1