Lidocaine Alleviates Sepsis-Induced Acute Lung Injury in Mice by Suppressing Tissue Factor and Matrix Metalloproteinase-2/9

Acute lung injury (ALI) is one of the fatal symptoms of sepsis. However, there were no effective clinical treatments. TF accumulation-induced fibrin deposit formations and coagulation abnormalities in pulmonary vessels contribute to the lethality of ALI. Suppressor of cytokine signaling 3 (SOCS3) ac...

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Autores principales: Binbin Zheng, Hongbo Yang, Jianan Zhang, Xueli Wang, Hao Sun, Fan Hu, Qian Li, Liping Jiang, Yue Su, Qilin Peng, Yulin Tang, Wen-Tao Liu, Xueming He, Yixin Fan, Xia Zhu
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Publicado: Hindawi Limited 2021
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Acceso en línea:https://doaj.org/article/24ba934bfb3d4514a68375a1eed78671
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spelling oai:doaj.org-article:24ba934bfb3d4514a68375a1eed786712021-11-22T01:11:14ZLidocaine Alleviates Sepsis-Induced Acute Lung Injury in Mice by Suppressing Tissue Factor and Matrix Metalloproteinase-2/91942-099410.1155/2021/3827501https://doaj.org/article/24ba934bfb3d4514a68375a1eed786712021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/3827501https://doaj.org/toc/1942-0994Acute lung injury (ALI) is one of the fatal symptoms of sepsis. However, there were no effective clinical treatments. TF accumulation-induced fibrin deposit formations and coagulation abnormalities in pulmonary vessels contribute to the lethality of ALI. Suppressor of cytokine signaling 3 (SOCS3) acts as an endogenous negative regulator of the TLR4/TF pathway. We hypothesized that inducing SOCS3 expression using lidocaine to suppress the TLR4/TF pathway may alleviate ALI. Hematoxylin and eosin (H&E), B-mode ultrasound, and flow cytometry were used to measure the pathological damage of mice. Gelatin zymography was used to measure matrix metalloproteinase-2/9 (MMP-2/9) activities. Western blot was used to assay the expression of protein levels. Here, we show that lidocaine could increase the survival rate of ALI mice and ameliorate the lung injury of ALI mice including reducing the edema, neutrophil infiltration, and pulmonary thrombosis formation and increasing blood flow velocity. Moreover, in vitro and in vivo, lidocaine could increase the expression of p-AMPK and SOCS3 and subsequently decrease the expression of p-ASK1, p-p38, TF, and the activity of MMP-2/9. Taken together, our study demonstrated that lidocaine could inhibit the TLR4/ASK1/TF pathway to alleviate ALI via activating AMPK-SOCS3 axis.Binbin ZhengHongbo YangJianan ZhangXueli WangHao SunFan HuQian LiLiping JiangYue SuQilin PengYulin TangWen-Tao LiuXueming HeYixin FanXia ZhuHindawi LimitedarticleCytologyQH573-671ENOxidative Medicine and Cellular Longevity, Vol 2021 (2021)
institution DOAJ
collection DOAJ
language EN
topic Cytology
QH573-671
spellingShingle Cytology
QH573-671
Binbin Zheng
Hongbo Yang
Jianan Zhang
Xueli Wang
Hao Sun
Fan Hu
Qian Li
Liping Jiang
Yue Su
Qilin Peng
Yulin Tang
Wen-Tao Liu
Xueming He
Yixin Fan
Xia Zhu
Lidocaine Alleviates Sepsis-Induced Acute Lung Injury in Mice by Suppressing Tissue Factor and Matrix Metalloproteinase-2/9
description Acute lung injury (ALI) is one of the fatal symptoms of sepsis. However, there were no effective clinical treatments. TF accumulation-induced fibrin deposit formations and coagulation abnormalities in pulmonary vessels contribute to the lethality of ALI. Suppressor of cytokine signaling 3 (SOCS3) acts as an endogenous negative regulator of the TLR4/TF pathway. We hypothesized that inducing SOCS3 expression using lidocaine to suppress the TLR4/TF pathway may alleviate ALI. Hematoxylin and eosin (H&E), B-mode ultrasound, and flow cytometry were used to measure the pathological damage of mice. Gelatin zymography was used to measure matrix metalloproteinase-2/9 (MMP-2/9) activities. Western blot was used to assay the expression of protein levels. Here, we show that lidocaine could increase the survival rate of ALI mice and ameliorate the lung injury of ALI mice including reducing the edema, neutrophil infiltration, and pulmonary thrombosis formation and increasing blood flow velocity. Moreover, in vitro and in vivo, lidocaine could increase the expression of p-AMPK and SOCS3 and subsequently decrease the expression of p-ASK1, p-p38, TF, and the activity of MMP-2/9. Taken together, our study demonstrated that lidocaine could inhibit the TLR4/ASK1/TF pathway to alleviate ALI via activating AMPK-SOCS3 axis.
format article
author Binbin Zheng
Hongbo Yang
Jianan Zhang
Xueli Wang
Hao Sun
Fan Hu
Qian Li
Liping Jiang
Yue Su
Qilin Peng
Yulin Tang
Wen-Tao Liu
Xueming He
Yixin Fan
Xia Zhu
author_facet Binbin Zheng
Hongbo Yang
Jianan Zhang
Xueli Wang
Hao Sun
Fan Hu
Qian Li
Liping Jiang
Yue Su
Qilin Peng
Yulin Tang
Wen-Tao Liu
Xueming He
Yixin Fan
Xia Zhu
author_sort Binbin Zheng
title Lidocaine Alleviates Sepsis-Induced Acute Lung Injury in Mice by Suppressing Tissue Factor and Matrix Metalloproteinase-2/9
title_short Lidocaine Alleviates Sepsis-Induced Acute Lung Injury in Mice by Suppressing Tissue Factor and Matrix Metalloproteinase-2/9
title_full Lidocaine Alleviates Sepsis-Induced Acute Lung Injury in Mice by Suppressing Tissue Factor and Matrix Metalloproteinase-2/9
title_fullStr Lidocaine Alleviates Sepsis-Induced Acute Lung Injury in Mice by Suppressing Tissue Factor and Matrix Metalloproteinase-2/9
title_full_unstemmed Lidocaine Alleviates Sepsis-Induced Acute Lung Injury in Mice by Suppressing Tissue Factor and Matrix Metalloproteinase-2/9
title_sort lidocaine alleviates sepsis-induced acute lung injury in mice by suppressing tissue factor and matrix metalloproteinase-2/9
publisher Hindawi Limited
publishDate 2021
url https://doaj.org/article/24ba934bfb3d4514a68375a1eed78671
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