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青蒿琥酯通过 Toll 样受体 4/核因子-κB 信号通路预防大鼠肾炎。

Effects of Artesunate prevent nephritis via the Toll‑like receptor 4/nuclear factor‑κB signaling pathway in rats.

机构信息

Department of Urology, Tianjin Nankai Hospital, Tianjin, Nankai 300100, P.R. China.

出版信息

Mol Med Rep. 2017 Nov;16(5):6389-6395. doi: 10.3892/mmr.2017.7362. Epub 2017 Aug 24.

Abstract

The active ingredient in Artemisia carvifolia, artemisinin, may alleviate inflammation and toxicity. Artemisinin and its derivatives are first‑line anti‑malarial drugs currently, which have rapid effects on fever caused by malaria parasites with fewer side effects. The present study investigated the effects of Artesunate in a mouse nephritis model. Mice were injected intraperitoneally with 500 µl pristine to induce nephritis, and were treated with 28.8 mg/kg Artesunate. Subsequently, proteinuria, renal function, and tumor necrosis factor (TNF)‑α and interleukin (IL)‑6 levels were assessed to evaluate the effects of Artesunate on nephritis. Western blot analysis was used to measure the protein expression levels of α‑smooth muscle actin (SMA), TLR4, myeloid differentiation primary response gene 88 (MyD88), NF‑κB p65 and transforming growth factor (TGF)‑β1 to investigate the underlying mechanisms of Artesunate on nephritis. The results demonstrated that Artesunate reduced proteinuria and preserved renal function in nephritis mice. Artesunate attenuated TNF‑α and IL‑6 levels, suppressed α‑SMA, TLR4, MyD88, NF‑κB p65 and TGF‑β1 protein expression, and decreased caspase‑3 activity in nephritis mice. These results indicated that the effects of Artesunate may prevent nephritis and inhibit inflammation via the TLR4/NF‑κB signaling pathway in mice. Therefore, Artesunate may be a potential therapeutic agent to prevent nephritis.

摘要

青蒿中的活性成分青蒿素可能具有抗炎和解毒作用。青蒿素及其衍生物是目前治疗疟疾的一线抗疟药物,对疟原虫引起的发热有快速作用,副作用较少。本研究探讨了青蒿琥酯在小鼠肾炎模型中的作用。通过腹腔注射 500µl pristimerin 诱导肾炎,并用 28.8mg/kg 青蒿琥酯治疗。随后,评估蛋白尿、肾功能以及肿瘤坏死因子(TNF)-α 和白细胞介素(IL)-6 水平,以评估青蒿琥酯对肾炎的影响。Western blot 分析用于测量 α-平滑肌肌动蛋白(SMA)、Toll 样受体 4(TLR4)、髓样分化初级反应基因 88(MyD88)、核因子-κB p65 和转化生长因子(TGF)-β1 的蛋白表达水平,以探讨青蒿琥酯对肾炎的潜在作用机制。结果表明,青蒿琥酯可减少肾炎小鼠的蛋白尿并保护肾功能。青蒿琥酯可降低 TNF-α 和 IL-6 水平,抑制 α-SMA、TLR4、MyD88、NF-κB p65 和 TGF-β1 蛋白表达,并降低肾炎小鼠 caspase-3 活性。这些结果表明,青蒿琥酯可能通过 TLR4/NF-κB 信号通路预防肾炎和抑制炎症,因此可能是预防肾炎的潜在治疗药物。

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