Heme Oxygenase-1 Reduces Sepsis-Induced Endoplasmic Reticulum Stress and Acute Lung Injury.
Heme Oxygenase-1 Reduces Sepsis-Induced Endoplasmic Reticulum Stress and Acute Lung Injury.
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血红素加氧酶 1 可减少脓毒症引起的内质网应激和急性肺损伤
DOI：
10.1155/2018/9413876
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发表时间：
2018
影响因子：
4.6
通讯作者：
Lian Q
中科院分区：
文献类型：
--
作者：
Chen X;Wang Y;Xie X;Chen H;Zhu Q;Ge Z;Wei H;Deng J;Xia Z;Lian Q
脓毒症导致严重的急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS），这与增强的内质网（ER）应激有关。血红素氧合酶-1（HO-1）是一种ER锚定蛋白，在ALI时发挥抗氧化和保护作用。然而，HO-1活化在脓毒症期间内质网（ER）应激发展中的作用仍不清楚。 建立盲肠结扎穿孔（CLP）模型，诱导脓毒性ALI。CLP后18小时测量肺组织ER应力。采用HO-1激动剂hemin和拮抗剂ZnPP在体内研究了HO-1在脓毒症ALI期间对ER应激的影响。 与假手术组相比，CLP后18小时脓毒症肺组织中ER应激显著增加，ER抑制剂4-苯基丁酸（4-PBA）预处理可显著降低脓毒症肺组织中ER应激。ER应激抑制后脓毒症大鼠肺损伤评分和肺湿/干（W/D）比值显著降低。同样，ER应激抑制后，肺ER应激相关基因（PERK，eIF 2-α，ATF 4和CHOP）的水平降低。此外，血红素激活HO-1可降低p-PERK、p-eIF 2-α、ATF 4和CHOP蛋白表达以及氧化应激和肺细胞凋亡。另外，HO-1拮抗剂可使ER应激相关的ALI聚集。 内质网应激在CLP诱导的ALI过程中被激活，这可能是CLP诱导ALI的机制之一。HO-1的激活可抑制CLP诱导的肺ER应激，减轻CLP诱导的ALI。
Sepsis leads to severe acute lung injury/acute respiratory distress syndrome (ALI/ARDS) that is associated with enhanced endoplasmic reticulum (ER) stress. Heme oxygenase-1 (HO-1), an ER-anchored protein, exerts antioxidant and protective functions under ALI. However, the role of HO-1 activation in the development of endoplasmic reticulum (ER) stress during sepsis remains unknown. Cecal ligation and puncture (CLP) model was created to induce septic ALI. Lung tissue ER stress was measured 18 hours after CLP. The effects of HO-1 on ER stress during septic ALI were investigated in vivo using HO-1 agonist hemin and antagonist ZnPP. Compared with the sham group, ER stress in septic lung increased significantly 18 hours after CLP, which was significantly reduced by pretreatment with the ER inhibitor 4-phenylbutyrate (4-PBA). The lung injury score and the lung wet to dry (W/D) ratio in lungs were significantly reduced in septic rats after ER stress inhibition. Similarly, lung ER stress-related genes' (PERK, eIF2-α, ATF4, and CHOP) levels were attenuated after ER stress inhibition. Furthermore, HO-1 activation by hemin reduced p-PERK, p-eIF2-α, ATF4, and CHOP protein expression and oxidative stress and lung cell apoptosis. Additionally, HO-1 antagonist could aggregate the ER stress-related ALI. ER stress was activated during CLP-induced ALI, which may represent a mechanism by which CLP induces ALI. HO-1 activation could inhibit CLP-induced lung ER stress and attenuate CLP-induced ALI.
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影响因子：
4.6
作者：
Kim, Hee Jung;Jeong, Jae Seok;Kim, So Ri;Park, Seung Yong;Chae, Han Jung;Lee, Yong Chul
通讯作者：
Lee, Yong Chul
影响因子：
5.5
作者：
Lindholm D;Korhonen L;Eriksson O;Kõks S
通讯作者：
Kõks S
尿源干细胞对鱼精蛋白/脂多糖诱导的间质性膀胱炎大鼠模型的治疗作用
影响因子：
7.5
作者：
Li J;Luo H;Dong X;Liu Q;Wu C;Zhang T;Hu X;Zhang Y;Song B;Li L
通讯作者：
Li L
影响因子：
--
作者：
Aziz, N M;Kamel, M Y;Rifaai, R A
通讯作者：
Rifaai, R A
DOI：
10.1016/j.bbrc.2017.05.173
发表时间：
2017-09-16
影响因子：
3.1
作者：
Gong, Yuanqi;Lan, Haibing;Shao, Jianghua
通讯作者：
Shao, Jianghua