宋佳, S. Jia, 王春霞, W. Chunxia, 熊熙, X. Xi, 任玉倩, R. Yuqian, 张育才, Z. Yucai
{"title":"甲基强的松龙通过抑制STAT3-ERK1/2信号通路减轻lps诱导的急性肺损伤","authors":"宋佳, S. Jia, 王春霞, W. Chunxia, 熊熙, X. Xi, 任玉倩, R. Yuqian, 张育才, Z. Yucai","doi":"10.3760/CMA.J.ISSN.1671-0282.2019.10.017","DOIUrl":null,"url":null,"abstract":"Objective \nTo investigate the effects of methylprednisolone on STAT3-ERK1/2 signaling pathway in lipopolysaccharide (LPS)-induced acute lung injury (ALI). \n \n \nMethods \nThe C57BL/6J male mice (8-week-old) were randomly(random number) divided into 4 groups: control group (control), LPS-induced endotoxemia model (LPS), only methylprednisolone (MP) administration group (MP), and intervention group with 2 mg/kg MP (LPS+MP) (n= 8 per group). The wet/dry (W/D) weight ratio of lung tissue, lung pathology by hematoxylin & eosin (HE) staining, serum and mRNA levels of TNF-α and IL-6 in lungs were determined. The protein levels of p-STAT3 and p-ERK1/2 in lungs were detected by Western blot. Statistical analyses were performed using One-way analysis of variance test to compare among multiple groups. \n \n \nResults \n(1)MP treatment significantly decreased the lung W/D weight ratio compared with the LPS group[(3.01±0.84) vs(3.87±0.17), P = 0.038]; (2) The histopathological lesions of the lung were improved in the LPS+MP group compared with the LPS group accompanied with reduced inflammatory cell infiltration and attenuated the alveolar wall thickening; (3) The serum levels of TNF-α and IL-6 in the LPS+MP group was significantly decreased compared with the LPS group[(3.17±1.64) pg/mL vs (6.61±1.27) pg/mL, P = 0.003; (1.42±0.35) pg/mL vs (3.80±1.35) pg/mL, P = 0.008, respectively], and the mRNA levels of TNF-α and IL-6 in the LPS+MP group were significantly lower than those of the LPS group [(5.10±0.81) vs (12.2±5.05), P = 0.03; (1.62±1.00) vs (11.12±6.56), P=0.026; respectively]; (4) MP therapy significantly inhibited P-STAT3 and P-ERK1/2 protein levels [(0.26±0.05) vs (0.86±0.06), P < 0.001, (0.24±0.02) vs (1.34±0.32), P < 0.001]. \n \n \nConclusions \nMethylprednisolone protects LPS-induced acute lung injury possibly via suppressing STAT3-ERK1/2 signaling pathway and reducing TNF-α and IL-6 expression. \n \n \nKey words: \nMethylprednisolone; STAT3; ERK1/2; Lipopolysaccharide; Acute lung injury; Sepsis; TNF-α; IL-6","PeriodicalId":9981,"journal":{"name":"中华急诊医学杂志","volume":"28 1","pages":"1266-1271"},"PeriodicalIF":0.0000,"publicationDate":"2019-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Methylprednisolone alleviates LPS-induced acute lung injury by inhibiting STAT3-ERK1/2 signaling pathway\",\"authors\":\"宋佳, S. Jia, 王春霞, W. Chunxia, 熊熙, X. Xi, 任玉倩, R. Yuqian, 张育才, Z. Yucai\",\"doi\":\"10.3760/CMA.J.ISSN.1671-0282.2019.10.017\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Objective \\nTo investigate the effects of methylprednisolone on STAT3-ERK1/2 signaling pathway in lipopolysaccharide (LPS)-induced acute lung injury (ALI). \\n \\n \\nMethods \\nThe C57BL/6J male mice (8-week-old) were randomly(random number) divided into 4 groups: control group (control), LPS-induced endotoxemia model (LPS), only methylprednisolone (MP) administration group (MP), and intervention group with 2 mg/kg MP (LPS+MP) (n= 8 per group). The wet/dry (W/D) weight ratio of lung tissue, lung pathology by hematoxylin & eosin (HE) staining, serum and mRNA levels of TNF-α and IL-6 in lungs were determined. The protein levels of p-STAT3 and p-ERK1/2 in lungs were detected by Western blot. Statistical analyses were performed using One-way analysis of variance test to compare among multiple groups. \\n \\n \\nResults \\n(1)MP treatment significantly decreased the lung W/D weight ratio compared with the LPS group[(3.01±0.84) vs(3.87±0.17), P = 0.038]; (2) The histopathological lesions of the lung were improved in the LPS+MP group compared with the LPS group accompanied with reduced inflammatory cell infiltration and attenuated the alveolar wall thickening; (3) The serum levels of TNF-α and IL-6 in the LPS+MP group was significantly decreased compared with the LPS group[(3.17±1.64) pg/mL vs (6.61±1.27) pg/mL, P = 0.003; (1.42±0.35) pg/mL vs (3.80±1.35) pg/mL, P = 0.008, respectively], and the mRNA levels of TNF-α and IL-6 in the LPS+MP group were significantly lower than those of the LPS group [(5.10±0.81) vs (12.2±5.05), P = 0.03; (1.62±1.00) vs (11.12±6.56), P=0.026; respectively]; (4) MP therapy significantly inhibited P-STAT3 and P-ERK1/2 protein levels [(0.26±0.05) vs (0.86±0.06), P < 0.001, (0.24±0.02) vs (1.34±0.32), P < 0.001]. \\n \\n \\nConclusions \\nMethylprednisolone protects LPS-induced acute lung injury possibly via suppressing STAT3-ERK1/2 signaling pathway and reducing TNF-α and IL-6 expression. \\n \\n \\nKey words: \\nMethylprednisolone; STAT3; ERK1/2; Lipopolysaccharide; Acute lung injury; Sepsis; TNF-α; IL-6\",\"PeriodicalId\":9981,\"journal\":{\"name\":\"中华急诊医学杂志\",\"volume\":\"28 1\",\"pages\":\"1266-1271\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2019-10-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"中华急诊医学杂志\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3760/CMA.J.ISSN.1671-0282.2019.10.017\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Nursing\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"中华急诊医学杂志","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3760/CMA.J.ISSN.1671-0282.2019.10.017","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Nursing","Score":null,"Total":0}
Objective
To investigate the effects of methylprednisolone on STAT3-ERK1/2 signaling pathway in lipopolysaccharide (LPS)-induced acute lung injury (ALI).
Methods
The C57BL/6J male mice (8-week-old) were randomly(random number) divided into 4 groups: control group (control), LPS-induced endotoxemia model (LPS), only methylprednisolone (MP) administration group (MP), and intervention group with 2 mg/kg MP (LPS+MP) (n= 8 per group). The wet/dry (W/D) weight ratio of lung tissue, lung pathology by hematoxylin & eosin (HE) staining, serum and mRNA levels of TNF-α and IL-6 in lungs were determined. The protein levels of p-STAT3 and p-ERK1/2 in lungs were detected by Western blot. Statistical analyses were performed using One-way analysis of variance test to compare among multiple groups.
Results
(1)MP treatment significantly decreased the lung W/D weight ratio compared with the LPS group[(3.01±0.84) vs(3.87±0.17), P = 0.038]; (2) The histopathological lesions of the lung were improved in the LPS+MP group compared with the LPS group accompanied with reduced inflammatory cell infiltration and attenuated the alveolar wall thickening; (3) The serum levels of TNF-α and IL-6 in the LPS+MP group was significantly decreased compared with the LPS group[(3.17±1.64) pg/mL vs (6.61±1.27) pg/mL, P = 0.003; (1.42±0.35) pg/mL vs (3.80±1.35) pg/mL, P = 0.008, respectively], and the mRNA levels of TNF-α and IL-6 in the LPS+MP group were significantly lower than those of the LPS group [(5.10±0.81) vs (12.2±5.05), P = 0.03; (1.62±1.00) vs (11.12±6.56), P=0.026; respectively]; (4) MP therapy significantly inhibited P-STAT3 and P-ERK1/2 protein levels [(0.26±0.05) vs (0.86±0.06), P < 0.001, (0.24±0.02) vs (1.34±0.32), P < 0.001].
Conclusions
Methylprednisolone protects LPS-induced acute lung injury possibly via suppressing STAT3-ERK1/2 signaling pathway and reducing TNF-α and IL-6 expression.
Key words:
Methylprednisolone; STAT3; ERK1/2; Lipopolysaccharide; Acute lung injury; Sepsis; TNF-α; IL-6
期刊介绍:
Chinese Journal of Emergency Medicine is the only national journal which represents the development of emergency medicine in China. The journal is supervised by China Association of Science and Technology, sponsored by Chinese Medical Association, and co-sponsored by Zhejiang University. The journal publishes original research articles dealing with all aspects of clinical practice and research in emergency medicine. The columns include Pre-Hospital Rescue, Emergency Care, Trauma, Resuscitation, Poisoning, Disaster Medicine, Continuing Education, etc. It has a wide coverage in China, and builds up communication with Hong Kong, Macao, Taiwan and international emergency medicine circles.