Emodin reactivated autophagy and alleviated inflammatory lung injury in mice with lethal endotoxemia
Emodin reactivated autophagy and alleviated inflammatory lung injury in mice with lethal endotoxemia
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DOI：
10.1538/expanim.19-0004
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发表时间：
2019-01-01
影响因子：
2.4
通讯作者：
Liu, Gang
中科院分区：
文献类型：
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作者：
Dong, Yan;Zhang, Li;Liu, Gang
急性肺损伤（acute lung injury， ALI）是一种不受控制的炎症引起严重的健康问题，具有严重的发病率和死亡率。最近的研究发现大黄素具有抗炎作用。在此，我们研究了大黄素对小鼠模型的潜在影响及致死剂量的潜在机制和脂多糖（LPS）诱导的小鼠炎性肺损伤。观察LPS作用后18 h肺组织异常、Evans蓝漏、髓过氧化物酶（MPO）活性、肺组织tnf - α、IL-6、一氧化氮（NO）、乳酸（LA）水平。Western blotting检测LC3-II与BECN1的表达情况。同时监测lps暴露小鼠的存活率。结果表明，大黄素干预对减轻lps诱导的肺组织组织学改变和lps诱导的Evans蓝渗漏具有重要作用，其与抑制MPO活性升高和抑制LA对肺组织中tnf - α、IL-6、NO的上调有关。此外，大黄素干预可提高lps暴露小鼠的存活率。最后，大黄素治疗增加了lps暴露小鼠肺中的LC3和BECN1。用3-MA（自噬抑制剂）治疗逆转了大黄素的有益作用。综上所述，大黄素可能对lps诱导的炎性肺损伤具有药理作用，其机制可能与自噬的恢复有关。
An uncontrolled inflammation induced critical health problems with serious morbidity and death, which namely acute lung injury (ALI). Recently researchs have found the anti-inflammatory effects of emodin. Here, we investigated the potential effects of emodin on a mouse model with a lethal dose of the potential mechanisms and lipopolysaccharide (LPS)-induced inflammatory lung injury in mice. The pulmonary histological abnormalities, the Evans blue's leakage, the myeloperoxidase (MPO) activity, the grades of TNF-alpha, IL-6, nitric oxide (NO), lactic acid (LA) in lung tissues were determined 18 h post exposure of LPS. Based on the expression of LC3-II with BECN1 was determined using Western blotting. Besides, the LPS-exposed mice for survival rate was monitored. The results indicated that intervention with emodin was important for mitigating LPS-induced pulmonary histological change and LPS-induced leakage of Evans blue, which were associated with suppressed elevation of MPO activity and inhibited up-regulation of TNF-alpha, IL-6, NO with LA in lung tissues. Moreover, intervention with emodin enhanced the survival rate of LPS-exposed mice. Finally, therapy with emodin increased the LC3 and BECN1 in lungs of LPS-exposed mice. Treatment with 3-MA (the autophagy inhibitor) reversed the beneficial effects of emodin. In conclusion, emodin might provide pharmacological benefits in LPS-induced inflammatory lung injury, and the mechanisms might be related to the restoration of autophagy.