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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2021
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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) |
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Cytology QH573-671 |
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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 |
work_keys_str_mv |
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