Mitochondrial DNA plays an important role in lung injury induced by sepsis
Mitochondrial DNA plays an important role in lung injury induced by sepsis
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线粒体DNA在脓毒症引起的肺损伤中发挥重要作用
DOI：
10.1002/jcb.28142
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发表时间：
2019-05-01
影响因子：
4
通讯作者：
Qian, Kejian
中科院分区：
文献类型：
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作者：
Zeng, Zhenguo;Li, Dan;Qian, Kejian
线粒体 DNA (mtDNA) 在脓毒症引起的肺损伤发展中的作用和机制尚不清楚。在我们目前的研究中，我们研究了 mtDNA 在脓毒症诱导的肺损伤模型中的体外和体内作用。与正常组相比，脂多糖（LPSs）组和mtDNA组的肺组织病理学评分、阳性凋亡细胞数、湿/干（W/D）比值以及TNF-α、IL-1β、IL-6浓度均显着升高（分别P < 0.001）。同时，LPS+mtDNA组和小干扰RNA（siRNA）-NC+LPS+mtDNA组的肺组织病理学评分、阳性W/D比值、凋亡细胞数以及肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-6浓度较LPS组显着上调（P < 0.05）。然而，与LPS组相比，Toll样受体（TLR9）siRNA + LPS + mtDNA组的肺组织病理学评分、阳性凋亡细胞数、W/D比值以及TNF-α、IL-1β和IL-6浓度均显着改善（P < 0.01）。 Western blot分析或免疫组化检测结果显示，LPS组和mtDNA组TLR9、MyD88、NF-κB蛋白或基因表达量较正常组显着上调（P < 0.01），且LPS+mtDNA组和siRNA-NC+LPS+mtDNA组TLR9、MyD88、NF-κB蛋白或基因表达量较LPS显着增强。组（P < 0.05，分别）。然而，与LPS组相比，TLR9siRNA+LPS+mtDNA组的TLR9、MyD88和NF-κB蛋白或基因表达显着受到抑制（分别P < 0.01）。总之，mtDNA 可通过体内外调节 TLR9/MyD88/NF-kappa B 通路引发脓毒症引起的肺损伤。
The effects and mechanisms of mitochondrial DNA (mtDNA) in the development of sepsis-induced lung injury is not well understood. In our present study, we studied the mtDNA effects in sepsis-induced lung injury model, in vitro and in vivo. Compared with the Normal group, the lung histopathological score, the number of positive apoptosis cell, wet/dry (W/D) ratio and TNF-alpha, IL-1 beta, and IL-6 concentrations of lipopolysaccharides (LPSs) and mtDNA groups were significantly increased (P < 0.001, respectively). Meanwhile, the lung histopathological score, positive W/D ratio, number of apoptosis cell and tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-6 concentrations of LPS + mtDNA and small interfering RNA (siRNA)-NC + LPS + mtDNA groups were significantly upregulated compared with those of LPS group (P < 0.05, respectively). However, the lung histopathological score, the number of positive apoptosis cell, W/D ratio and TNF-alpha, IL-1 beta, and IL-6 concentrations were significantly improved within the toll-like receptor (TLR9)siRNA + LPS + mtDNA group compared with the LPS group (P < 0.01, respectively). The TLR9, MyD88, and NF-kappa B proteins or gene expressions of the LPS group and mtDNA group were significantly upregulated compared with those of Normal group by Western blot analysis or immunohistochemistry assay (P < 0.01, respectively), and the TLR9, MyD88, and NF-kappa B proteins or gene expressions of LPS + mtDNA and siRNA-NC + LPS + mtDNA groups were significantly enhanced compared with those of LPS group (P < 0.05, respectively). However, the TLR9, MyD88, and NF-kappa B proteins or gene expressions of TLR9siRNA + LPS + mtDNA group were significantly suppressed compared with those of the LPS group (P < 0.01, respectively). In conclusion, mtDNA could provoke lung injury induced by sepsis via regulation of TLR9/MyD88/NF-kappa B pathway in vitro and in vivo.