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帕瑞昔布通过调节丝裂原活化蛋白激酶(MAPK)信号通路减轻脓毒症H9c2细胞的炎症损伤。

Parecoxib attenuates inflammation injury in septic H9c2 cells by regulating the MAPK signaling pathway.

作者信息

Qian Xin, Xiong Shijuan, Chen Qi, Zhang Jiaxing, Xie Juan

机构信息

Department of Pharmacy, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550000, P.R. China.

出版信息

Exp Ther Med. 2023 Feb 16;25(4):150. doi: 10.3892/etm.2023.11850. eCollection 2023 Apr.

DOI:10.3892/etm.2023.11850
PMID:36911374
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9995842/
Abstract

Parecoxib, a non-steroidal anti-inflammatory drug, has been reported to possess protective effects against sepsis. However, its detailed role and underlying mechanisms in septic cardiomyopathy remain unclear. Therefore, the goal of the present study was to clarify the function and to investigate the mechanisms of parecoxib in lipopolysaccharide (LPS)-treated H9c2 rat cardiomyocytes. TNF-α, IL-1β and IL-6 expression levels in parecoxib-treated H9c2 cells stimulated with LPS were assessed using ELISA. Parecoxib-treated H9c2 cells stimulated with LPS were tested for viability using the Cell Counting Kit-8 assay. Western blotting analysis and 5-ethynyl-2'-deoxyuridine were used to evaluate cell proliferation. Apoptosis was assessed using TUNEL and western blotting. To assess the protein expression of the MAPK signaling pathway, western blotting was performed. The data showed that parecoxib significantly and dose-dependently reduced the inflammatory responses of LPS-treated H9c2 cells. Parecoxib also significantly and dose-dependently increased the proliferation and inhibited the apoptosis of LPS-treated H9c2 cells. In addition, parecoxib significantly suppressed the activation of the MAPK (p38, JNK and ERK) signaling pathway. The current study indicated that parecoxib could be a viable therapeutic option for septic cardiomyopathy.

摘要

帕瑞昔布是一种非甾体类抗炎药,据报道具有抗败血症的保护作用。然而,其在脓毒性心肌病中的具体作用和潜在机制仍不清楚。因此,本研究的目的是阐明帕瑞昔布在脂多糖(LPS)处理的H9c2大鼠心肌细胞中的功能并探究其机制。使用酶联免疫吸附测定法评估用帕瑞昔布处理并用LPS刺激的H9c2细胞中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的表达水平。使用细胞计数试剂盒-8检测法检测用帕瑞昔布处理并用LPS刺激的H9c2细胞的活力。采用蛋白质免疫印迹分析和5-乙炔基-2'-脱氧尿苷评估细胞增殖。使用末端脱氧核苷酸转移酶介导的缺口末端标记法(TUNEL)和蛋白质免疫印迹法评估细胞凋亡。为了评估丝裂原活化蛋白激酶(MAPK)信号通路的蛋白质表达,进行了蛋白质免疫印迹分析。数据显示,帕瑞昔布显著且剂量依赖性地降低了LPS处理的H9c2细胞的炎症反应。帕瑞昔布还显著且剂量依赖性地增加了LPS处理的H9c2细胞的增殖并抑制了其凋亡。此外,帕瑞昔布显著抑制了MAPK(p38、c-Jun氨基末端激酶(JNK)和细胞外信号调节激酶(ERK))信号通路的激活。目前的研究表明,帕瑞昔布可能是脓毒性心肌病的一种可行治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1aa/9995842/09c5b3af8cb9/etm-25-04-11850-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1aa/9995842/96f456187cad/etm-25-04-11850-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1aa/9995842/0f65fb8787e8/etm-25-04-11850-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1aa/9995842/03e60a3fe913/etm-25-04-11850-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1aa/9995842/09c5b3af8cb9/etm-25-04-11850-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1aa/9995842/96f456187cad/etm-25-04-11850-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1aa/9995842/0f65fb8787e8/etm-25-04-11850-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1aa/9995842/03e60a3fe913/etm-25-04-11850-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1aa/9995842/09c5b3af8cb9/etm-25-04-11850-g03.jpg

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