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首页> 外文期刊>European Journal of Pharmacology: An International Journal >Harmine mitigates LPS-induced acute kidney injury through inhibition of the TLR4-NF-kappa B/NLRP3 inflammasome signalling pathway in mice
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Harmine mitigates LPS-induced acute kidney injury through inhibition of the TLR4-NF-kappa B/NLRP3 inflammasome signalling pathway in mice

机译：通过抑制小鼠的TLR4-NF-Kappa B / NLRP3炎性信号传导途径来缓解LPS诱导的急性肾损伤

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摘要

Acute kidney injury is a common clinical condition associated with increased morbidity and mortality. It is essential to find effective drugs with low side effects in the treatment of acute kidney injury. Harmine is one of the major active components of Peganum harmala L. Harmine possesses various pharmacological activities, including anti-inflammatory activity. Nevertheless, the protective effect of harmine in acute kidney injury induced by lipopolysaccharide (LPS) in mice is unknown. Therefore, we investigated the protective effect of harmine in LPS-induced renal inflammation and the involved molecular mechanisms. The results showed that pretreatment with harmine (25 or 50 mg/kg) markedly alleviated kidney injury by reducing the release of kidney biomarkers and inflammatory mediators and the formation of malondialdehyde (MDA) and myeloperoxidase (MPO) while increasing superoxide dismutase (SOD) and glutathione (GSH) activities and improving renal histopathological changes. In addition, immunohistochemistry staining and western blot analysis indicated that harmine treatment suppressed the expression of toll-like receptor 4 (TLR4) and the phosphorylation of nuclear factor-kappa B (NF-kappa B) p65 and inhibitor of kappa B alpha (I kappa B alpha) while inhibiting the expression of NLRP3, caspase-1 and interleukin-1 beta (IL-1 beta). In brief, harmine protects against acute kidney injury induced by LPS in mice through reducing oxidative stress and inflammation responses. The involved underlying mechanisms of harmine in LPS-induced acute kidney injury might be related to inhibition of the TLR4-NF-kappa B pathway and NLRP3 inflammasome pathway. Based on the above conclusion, it is possible for harmine to be used to clinically treat acute kidney injury.
机译：急性肾损伤是一种与发病率和死亡率增加相关的常见临床病症。在治疗急性肾损伤时，必须找到具有低副作用的有效药物。 Harnine是Peganum Harmala L. Harmine的主要活性组成部分之一，具有各种药理学活动，包括抗炎活动。然而，脂多糖（LPS）在小鼠中诱导的急性肾损伤的保护作用是未知的。因此，我们研究了HARANE在LPS诱导的肾炎中的保护作用和所涉及的分子机制。结果表明，通过降低肾脏生物标志物和炎症介质的释放以及形成丙二醛（MDA）和髓氧化酶（MPO）的形成，对肾脏生物标志物和炎症介质（MPO）的形成具有显着缓解肾损伤的预处理显着缓解了肾损伤。谷胱甘肽（GSH）活动和改善肾组织病理学变化。此外，免疫组织化学染色和蛋白质印迹分析表明，问题治疗抑制了Toll样受体4（TLR4）的表达和核因子-Kappa B（NF-Kappa B）P65和KappaBα的抑制剂（I Kappa）的磷酸化（I Kappa Bα）抑制NLRP3，Caspase-1和白细胞介素-1β（IL-1β）的表达。简而言之，通过降低氧化应激和炎症反应，对大鼠引起的LPS诱导的急性肾损伤。 LPS诱导的急性肾损伤的涉及的潜在机制可能与TLR4-NF-Kappa B途径和NLRP3炎症途径的抑制有关。基于上述结论，有可能用于临床治疗急性肾损伤。

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