Neutrophil Elastase Inhibitors Suppress Oxidative Stress in Lung during Liver Transplantation
Neutrophil Elastase Inhibitors Suppress Oxidative Stress in Lung during Liver Transplantation
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中性粒细胞弹性蛋白酶抑制剂抑制肝移植期间肺的氧化应激
DOI：
10.1155/2019/7323986
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发表时间：
2019-11
期刊：
影响因子：
--
通讯作者：
Ziqing Hei
中科院分区：
文献类型：
--
作者：
Weifeng Yao;Xue Han;Yu Guan;Jianqiang Guan;Shan Wu;Chaojin Chen;Haobo Li;Ziqing Hei
背景肝移植术后急性肺损伤的发生与神经细胞浸润密切相关。中性粒细胞弹性蛋白酶在肺多形性中性粒细胞活化和隔离期间从中性粒细胞释放。目的：探讨抑制中性粒细胞弹性蛋白酶是否能恢复LT后肺功能。方法：在体实验中，取大鼠原位自体LT（OALT）后2、4、8、24 h的肺组织和支气管肺泡灌洗液（BALF），检测中性粒细胞浸润情况。接着，在OALT前向大鼠给予中性粒细胞弹性蛋白酶抑制剂西维来司钠水合物（外源性）和丝氨酸蛋白酶抑制剂家族B成员1（SERPINB 1）（内源性），并在OALT后8 h测量中性粒细胞浸润、肺氧化应激和屏障功能。结果OALT致伤后2 h开始出现明显的中性粒细胞浸润，8 h达高峰，表现为萘酚阳性细胞数、BALF中性粒细胞弹性蛋白酶活性和肺髓过氧化物酶活性增加。中性粒细胞弹性蛋白酶抑制剂西维来司钠水合物或SERPINB 1治疗可有效减少肺萘酚阳性细胞和BALF炎性细胞含量，增加肺HO-1和紧密连接蛋白ZO-1和occludin的表达，并增加超氧化物歧化酶的活性。结论神经弹性蛋白酶抑制剂西维来司钠和SERPINB 1均能减少肺中性粒细胞浸润和肺氧化应激，最终恢复肺屏障功能。
Background Neutrophil infiltration plays a critical role in the pathogenesis of acute lung injury following liver transplantation (LT). Neutrophil elastase is released from neutrophils during pulmonary polymorphonuclear neutrophil activation and sequestration. The aim of the study was to investigate whether the inhibition of neutrophil elastase could lead to the restoration of pulmonary function following LT. Methods In in vivo experiments, lung tissue and bronchoalveolar lavage fluid (BALF) were collected at 2, 4, 8, and 24 h after rats were subjected to orthotopic autologous LT (OALT), and neutrophil infiltration was detected. Next, neutrophil elastase inhibitors, sivelestat sodium hydrate (exogenous) and serpin family B member 1 (SERPINB1) (endogenous), were administered to rats before OALT, and neutrophil infiltration, pulmonary oxidative stress, and barrier function were measured at 8 h after OALT. Results Obvious neutrophil infiltration occurred from 2 h and peaked at 8 h in the lungs of rats after they were subjected to OALT, as evidenced by an increase in naphthol-positive cells, BALF neutrophil elastase activity, and lung myeloperoxidase activity. Treatment with neutrophil elastase inhibitors, either sivelestat sodium hydrate or SERPINB1, effectively reduced lung naphthol-positive cells and BALF inflammatory cell content, increased expression of lung HO-1 and tight junction proteins ZO-1 and occludin, and increased the activity of superoxide dismutase. Conclusion Neutrophil elastase inhibitors, sivelestat sodium hydrate and SERPINB1, both reduced lung neutrophil infiltration and pulmonary oxidative stress and finally restored pulmonary barrier function.
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DOI：
10.1152/ajplung.2001.281.3.l556
发表时间：
2001-09
期刊：
American journal of physiology. Lung cellular and molecular physiology
影响因子：
--
作者：
K. Aoshiba;Kimihiko Yasuda;S. Yasui;J. Tamaoki;A. Nagai
通讯作者：
K. Aoshiba;Kimihiko Yasuda;S. Yasui;J. Tamaoki;A. Nagai
SERPINB1 通过 ERK1/2 介导的 STAT3 依赖性 HO-1 诱导改善肝移植中的急性肺损伤
影响因子：
7.4
作者：
Yao, Weifeng;Li, Haobo;Hei, Ziqing
通讯作者：
Hei, Ziqing
MG53通过dysferlin锚定在细胞膜上减少体内和体外缺血/再灌注损伤诱导的肝细胞凋亡
影响因子：
5.3
作者：
Yao W;Li H;Han X;Chen C;Zhang Y;Tai WL;Xia Z;Hei Z
通讯作者：
Hei Z
异丙酚通过抑制连接蛋白 32 组成的间隙连接减轻原位肝移植后的急性肾损伤。
影响因子：
8.8
作者：
Luo, Chenfang;Yuan, Dongdong;Hei, Ziqing
通讯作者：
Hei, Ziqing
影响因子：
56.9
作者：
Wang, Jing;Hossain, Mokarram;Kubes, Paul
通讯作者：
Kubes, Paul