Methane-Rich Saline Protects Against Sepsis-Induced Liver Damage by Regulating The PPAR-γ/NF-κB Signaling Pathway.
Methane-Rich Saline Protects Against Sepsis-Induced Liver Damage by Regulating The PPAR-γ/NF-κB Signaling Pathway.
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富甲烷生理盐水通过调节PPAR-γ/NF-κB信号通路保护脓毒症诱导的肝损伤
DOI：
10.1097/shk.0000000000001310
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发表时间：
2019-12
期刊：
影响因子：
3.1
通讯作者：
Zeyu Li;Yifan Jia;Yang Feng;Ruixia Cui;Zi Wang;K. Qu;Chang Liu;Jingyao Zhang
中科院分区：
文献类型：
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作者：
Zeyu Li;Yifan Jia;Yang Feng;Ruixia Cui;Zi Wang;K. Qu;Chang Liu;Jingyao Zhang
脓毒症是由于对感染的反应失调而导致的危及生命的器官功能障碍，是大手术的常见并发症。以前的研究表明，甲烷具有保护性能。本研究旨在探讨富甲烷盐水（MRS）对脓毒症肝损伤的保护作用。在体内实验中，C57 BL/6小鼠接受盲肠结扎和穿刺以建立脓毒症模型，随后在手术后30分钟和12小时进行MRS治疗（10 ml/kg，ip治疗）。结果表明，甲烷能有效降低血清谷草转氨酶、谷丙转氨酶和肝脏指数，减轻肝脏病理损伤，减少局部炎性细胞浸润。甲烷可抑制TLR 4/ NF-κB信号通路的表达，刺激PPAR-γ的表达，从而抑制NF-κB的活化，降低TNF-α、IL-6和IL-1β等炎症细胞因子的水平。此外，我们发现MRS处理通过上调血红素氧合酶-1、超氧化物歧化酶和谷胱甘肽，下调丙二醛来减轻ROS损伤，这与DHE荧光染色的结果一致。MRS治疗还调节了凋亡相关蛋白，如Bax，Bcl-2和caspase-3。在体外实验中，HepG 2细胞接受LPS诱导的炎症刺激，然后接受富甲烷培养基（MRM）处理。结果表明，MRM可减轻炎症损伤，减轻ROS损伤，并可调节PPAR-γ/NF-κB的表达。我们的数据表明，甲烷治疗通过抗炎，抗氧化和抗凋亡特性，涉及到过氧化物酶体增殖物激活受体-γ/核因子-κB信号通路，预防脓毒症肝损伤。
Sepsis, a life-threatening organ dysfunction due to a dysregulated response to infection, is a common complication of major surgery. Previous studies have showed that methane possesses protective properties. This study aims to investigate the protective effect of methane-rich saline (MRS) on sepsis-induced liver injury. In an in vivo experiment, C57BL/6 mice received cecal ligation and puncture to create a septic model followed by MRS treatment (10 ml/kg, ip treatment) 30 min and 12 h after the operation. We found that methane effectively decreased the serum aspartate aminotransferase, alanine aminotransferase and liver index, as well as the liver pathological damage, and reduced the localized infiltration of inflammatory cells. Methane suppressed the expression of the TLR4/ NF-κB signaling pathway and stimulated the expression of PPAR-γ during sepsis, which inhibited the activation of NF-κB and decreased the level of inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6 and interleukin-1β. Moreover, we found that MRS treatment relieved ROS damage by upregulating heme oxygenase-1, superoxide dismutase and glutathione, and downregulating malondialdehyde, which was consistent with the results of DHE fluorescent staining. MRS treatment also regulated apoptosis-related proteins, such as Bax, Bcl-2 and caspase-3. In the in vitro experiment, HepG2 cells received inflammatory stimulation induced by LPS followed by methane-rich medium (MRM) treatment. We found that MRM alleviated the inflammatory damage, ROS damage and regulated the expression of PPAR-γ/NF-κB. Our data indicated that methane treatment prevented liver damage in sepsis via anti-inflammatory, anti-oxidative, and anti-apoptotic properties that involved the PPAR-γ/ NF-κB signaling pathway.