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Brazilin exerts protective effects against renal ischemia-reperfusion injury by inhibiting the NF-κB signaling pathway

机译:Brazilin通过抑制NF-κB信号通路对肾脏缺血再灌注损伤发挥保护作用

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摘要

Renal ischemia-reperfusion (I/R) injury is associated with high morbidity and mortality as there is currently no available effective therapeutic strategy with which to treat this injury. Thus, the aim of this study was to investigate the potential protective effects of brazilin, a major active component of the Chinese medicine Caesalpinia sappan L., against renal I/R injury in vitro and in vivo. Rats were subjected to removal of the right kidney and I/R injury to the left kidney (ischemia for 45 min followed by reperfusion for 24 h). Treatment with brazilin (30 mg/kg, administered intravenously at 30 min prior to ischemia) led to the reversal of I/R-induced changes in serum creatinine (Scr) and blood urea nitrogen (BUN) levels, and also attenuated the histopathological damage induced by I/R. Furthermore, TUNEL assay revealed that brazilin reduced cell necrosis, and significantly decreased the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in renal tissue. Moreover, HK-2 cells were used in order to elucidate the mechanisms responsible for the protective effects of brazilin. The levels of phosphorylated IκBα and the nuclear translocation of nuclear factor-κB (NF-κB) were all evidently decreased by brazilin. These findings suggested that pre-treatment with brazilin protects against I/R-induced renal damage and suppresses the inflammatory response by inhibiting the activation of the NF-κB signaling pathway.
机译:肾缺血再灌注(I / R)损伤与高发病率和高死亡率相关,因为目前尚无可用的有效治疗策略来治疗这种损伤。因此,本研究的目的是研究巴西中草药Caesalpinia sappan L.的主要活性成分巴西对体外和体内对肾脏I / R损伤的潜在保护作用。对大鼠进行右肾的切除和左肾的I / R损伤(缺血45分钟,然后再灌注24小时)。用巴西唑(30 mg / kg,在缺血前30分钟静脉内给药)治疗可逆转I / R诱导的血清肌酐(Scr)和血尿素氮(BUN)水平的变化,并减轻组织病理学损害由I / R引起。此外,TUNEL分析表明,巴西林减少了细胞坏死,并显着降低了肾组织中肿瘤坏死因子(TNF)-α和白介素(IL)-1β的表达。此外,使用HK-2细胞来阐明负责巴西林保护作用的机制。巴西林明显降低了磷酸化的IκBα水平和核因子-κB(NF-κB)的核易位。这些发现表明,用巴西青霉素进行的预处理可预防I / R引起的肾脏损害,并通过抑制NF-κB信号通路的激活来抑制炎症反应。

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