OBJECTIVE To investigate the impact of death-associated protein kinase 1 (Dapk1) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) via p38MAPK/NF-κB pathway. METHODS Dapk1+/+ and Dapk1-/- mice were randomized into Control, LPS, SB203580 (a p38MAPK pathway inhibitor) + LPS, and PDTC (a NF-κB pathway inhibitor) + LPS groups. Cell counts, lung wet to dry weight ratio (W/D weight ratio), as well as indicators of oxidative stress were determined followed by the detection with HE staining, ELISA, qRT-PCR, Western blotting and Immunofluorescence. Besides, to explore whether the effect of Dapk1 on ALI directly mediated via p38MAPK/NF-κB pathway, mice were injected with TC-DAPK 6 (a Dapk1 inhibitor) with or without SB203580/PDTC before LPS administration. RESULTS LPS induced lung injury with increased lung W/D weight ratio, which could be partly reversed by SB203580 and PDTC in LPS-induced mice with activated p38MAPK/NF-κB pathway in lung tissues, especially in Dapk1-/- mice. SB203580 and PDTC reduced total cells and neutrophils in BALF in LPS-induced mice, accompanying with decreased levels of TNF-α, IL-6, MPO, LPO and MDA and the expressions of beclin-1, Atg5 and LC3II, but with the up-regulated activities of SOD and GSH-Px, as well as p62 protein expression. Besides, TC-DAPK 6 aggravated the pathologic injury in LPS-induced ALI with more serious inflammatory response, oxidative stress and autophagy as well as the activated p38MAPK/NF-κB pathway, which were reversed by SB203580 or PDTC. CONCLUSION Dapk1 improved oxidative stress, inhibited autophagy, and reduce inflammatory response of LPS-induced ALI mice by inhibiting p38MAPK/NF-κB pathway.

中文翻译：

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Dapk1通过p38MAPK /NF-κB信号通路改善LPS诱导的急性肺损伤中的炎症，氧化应激和自噬。

目的通过p38MAPK /NF-κB途径研究死亡相关蛋白激酶1（Dapk1）对脂多糖（LPS）诱导的急性肺损伤（ALI）的影响。方法将Dapk1 + / +和Dapk1-/-小鼠随机分为对照组，LPS，SB203580（p38MAPK途径抑制剂）+ LPS和PDTC（NF-κB途径抑制剂）+ LPS组。确定细胞计数，肺干重比（W / D重量比）以及氧化应激指标，然后通过HE染色，ELISA，qRT-PCR，Western印迹和免疫荧光检测。此外，为了研究Dapk1对p38MAPK /NF-κB途径直接介导的ALI的影响，在给予LPS之前，给小鼠注射TC-DAPK 6（一种Dapk1抑制剂），含或不含SB203580 / PDTC。结果LPS诱发的肺损伤伴有肺W / D重量比增加，在肺组织中，特别是在Dapk1-/-小鼠中，LPS诱导的具有激活的p38MAPK /NF-κB通路的LPS诱导的小鼠，其可能被SB203580和PDTC逆转。SB203580和PDTC减少LPS诱导的小鼠BALF中的总细胞和中性粒细胞，同时降低TNF-α，IL-6，MPO，LPO和MDA的水平以及beclin-1，Atg5和LC3II的表达，但随着调节SOD和GSH-Px的活性，以及​​p62蛋白的表达。此外，TC-DAPK 6加剧了LPS诱导的ALI的病理损伤，其炎症反应，氧化应激和自噬作用更为严重，并且激活的p38MAPK /NF-κB途径也被SB203580或PDTC所逆转。结论Dapk1通过抑制p38MAPK /NF-κB途径改善了LPS诱导的ALI小鼠的氧化应激，抑制了自噬并降低了炎症反应。