Dihydroartemisinin ameliorates sepsis-induced hyperpermeability of glomerular endothelium via up-regulation of occludin expression
Dihydroartemisinin ameliorates sepsis-induced hyperpermeability of glomerular endothelium via up-regulation of occludin expression
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DOI：
10.1016/j.biopha.2018.01.078
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发表时间：
2018-03-01
影响因子：
7.5
通讯作者：
Liu, Ju
中科院分区：
文献类型：
--
作者：
Cheng, Zuowang;Qi, Ruixia;Liu, Ju
脓毒症，感染后的全身炎症反应，仍然是危重患者发病和死亡的一个严重原因。抗疟疾药双氢青蒿素（DHA）已被证明具有抗炎作用。在这项研究中，我们研究了DHA对脓毒症诱导的急性肾损伤（AKI）的影响，并探讨了其在AKI中的作用机制。在脂多糖（LPS）诱导的小鼠模型中，我们观察到DHA治疗改善了肾小球损伤，缓解了尿白蛋白/肌酐比（UACR）和血清肌酐的升高。在25 μ M浓度下，DHA对人肾小球内皮细胞（HRGEC）的总体细胞活力和凋亡没有影响，但能显著抑制肿瘤坏死因子- α (tnf - α)诱导的HRGEC单层细胞的高通透性。我们发现tnf - α降低了hrgec中连接蛋白occludin的表达，而DHA则逆转了这一现象。综上所述，我们的研究结果表明DHA通过维持occludin的表达来降低肾小球内皮的通透性。这表明DHA可能对脓毒症引起的AKI有治疗作用。
Sepsis, the systemic inflammatory responses after infection, remains a serious cause of morbidity and mortality in critically ill patients. The anti-malarial agent dihydroartemisinin (DHA) has been shown to be anti-inflammatory. In this study, we examined the effects of DHA on sepsis-induced acute kidney injury (AKI) and explored the mechanism underlying its mode of action in AKI. In a lipopolysaccharide (LPS)-induced mouse model, we observed that DHA treatment ameliorated glomerular injury, and relieved elevation of the urine albumin to creatinine ratio (UACR) and serum creatinine. At a concentration of 25 mu M, DHA had no effect on overall cellular viability or apoptosis in assays with human renal glomerular endothelial cells (HRGECs), but significantly inhibited the tumor necrosis factor-alpha (TNF-alpha)-induced hyperpermeability of HRGEC monolayers. We found that TNF-alpha decreases the expression of the junctional protein occludin in HRGECs, which is reversed by DHA. Taken together, our results demonstrate that DHA decreases permeability of the glomerular endothelium by maintenance of occludin expression. This suggests DHA may have therapeutic utility in sepsis-induced AKI.