TNF-α- Mediated-p38-Dependent Signaling Pathway Contributes to Myocyte Apoptosis in Rats Subjected to Surgical Trauma
TNF-α- Mediated-p38-Dependent Signaling Pathway Contributes to Myocyte Apoptosis in Rats Subjected to Surgical Trauma
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DOI：
10.1159/000373965
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发表时间：
2015-03
影响因子：
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通讯作者：
Huaxing Wu;Guonian Wang;Shuai Li;Mingyue Zhang;Hulun Li;Kun-Kun Wang-Kun
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文献类型：
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作者：
Huaxing Wu;Guonian Wang;Shuai Li;Mingyue Zhang;Hulun Li;Kun-Kun Wang-Kun
背景：创伤后血浆中细胞因子的积累可诱导心肌细胞凋亡。我们的目的是确定哪些细胞因子存在于血浆中负责心肌细胞凋亡，并描绘了在大鼠手术创伤的信号转导机制。研究方法：将大鼠随机分为对照组和创伤组，创伤组又分为创伤后0、3、6、12和24 h亚组。将从创伤大鼠分离的心肌细胞与其中一种因子（正常血浆; Cytomix; TNF-α; IL-1β; IFN-γ;创伤血浆;抗TNF-α抗体; SB 203580）孵育12 h。以TUNEL法、流式细胞术、ELISA法和Western blot法分别检测心肌细胞凋亡、细胞因子水平和MAPKs活性。结果：手术创伤可在创伤后早期诱导心肌细胞凋亡。伴随着这种变化，创伤大鼠血浆TNF-α、IL-1β和IFN-γ水平升高。单独用cytomix或TNF-α孵育创伤的心肌细胞可诱导心肌细胞凋亡，并增加p38和ERK 1/2的活化。在创伤血浆中，创伤心肌细胞的凋亡和p38激活增加，抗TNF-α抗体或SB 203580可部分消除这些增加。结论：我们的研究表明，创伤后大鼠心肌细胞存在TNF-α介导的p38依赖性信号通路，该通路参与了创伤后心肌细胞凋亡。
Background: The accumulation of cytokines in the plasma after trauma can induce myocyte apoptosis. We aimed to identify which cytokine(s) present in the plasma responsible for myocyte apoptosis, and delineated the signal transduction mechanism in rats subjected to surgical trauma. Methods: Rats were randomized into two groups: control and trauma groups, which was divided into five subgroups: posttraumatic 0, 3, 6, 12, and 24 h subgroups. Cardiomyocytes isolated from traumatized rats were incubated with one of the factors for 12 h (normal plasma; Cytomix; TNF-α; IL-1β; IFN-γ; trauma plasma; anti-TNF-α antibody; SB203580). Myocyte apoptosis, cytokine levels, and MAPKs activation, as the primary experimental outcomes, were measured by TUNEL, flow cytometry, ELISA and Western blot, respectively. Results: Myocyte apoptosis was induced by surgical trauma during the early stage after trauma. Accompanying this change, plasma TNF-α, IL-1β, and IFN-γ levels were elevated in traumatized rats. Incubation of traumatized cardiomyocytes with cytomix or TNF-α alone induced myocyte apoptosis, and increased the activation of p38 and ERK1/2. Myocyte apoptosis and p38 activation were elevated in traumatized cardiomyocytes with trauma plasma, and these increases were partly abolished by anti-TNF-α antibody or SB203580. Conclusion: Our study demonstrated that there exists the TNF-α-mediated-p38-dependent signaling pathway that contributed to posttraumatic myocyte apoptosis of rats undergoing surgical trauma.