Ethyl pyruvate ameliorates hepatic ischemia-reperfusion injury by inhibiting intrinsic pathway of apoptosis and autophagy.
Ethyl pyruvate ameliorates hepatic ischemia-reperfusion injury by inhibiting intrinsic pathway of apoptosis and autophagy.
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DOI：
10.1155/2013/461536
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发表时间：
2013
影响因子：
4.6
通讯作者：
Guo C
中科院分区：
文献类型：
--
作者：
Shen M;Lu J;Dai W;Wang F;Xu L;Chen K;He L;Cheng P;Zhang Y;Wang C;Wu D;Yang J;Zhu R;Zhang H;Zhou Y;Guo C
背景。肝缺血再灌注（I/R）损伤是许多临床情况中发生的关键临床问题，例如移植、创伤和失血性休克后的肝功能衰竭。细胞凋亡和自噬已被证明会导致肝缺血再灌注损伤中的细胞死亡。丙酮酸乙酯是一种稳定且简单的亲脂性酯，已被证明具有抗炎特性。本研究旨在探讨丙酮酸乙酯对肝缺血再灌注损伤的影响以及对细胞凋亡和自噬内在途径的调节。 方法。 Balb/c小鼠建立节段性(70%)肝热缺血模型前1小时给予三种剂量的丙酮酸乙酯(20mg/kg、40mg/kg和80mg/kg)。所有血清和肝组织均在三个不同时间点（4小时、8小时和16小时）获得。 结果。丙酮酸乙酯（80mg/kg）显着改善丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和病理特征。 Bcl-2、Bax、Beclin-1 和 LC3 的表达在细胞凋亡和自噬的内在途径的调节中起重要作用，丙酮酸乙酯（80mg/kg）也明显降低了这些蛋白的表达。此外，丙酮酸乙酯抑制 HMGB1/TLR4/NF-κb 轴和细胞因子（TNF-α 和 IL-6）的释放。 结论。我们的结果表明，丙酮酸乙酯可能通过抑制细胞凋亡和自噬的内在途径来减轻肝缺血再灌注损伤，部分介导是通过下调 HMGB1/TLR4/NF-κb 轴以及与 HMGB1 的 Beclin-1 的竞争性相互作用来介导。
Background. Hepatic ischemia-reperfusion (I/R) injury is a pivotal clinical problem occurring in many clinical conditions such as transplantation, trauma, and hepatic failure after hemorrhagic shock. Apoptosis and autophagy have been shown to contribute to cell death in hepatic I/R injury. Ethyl pyruvate, a stable and simple lipophilic ester, has been shown to have anti-inflammatory properties. In this study, the purpose is to explore both the effect of ethyl pyruvate on hepatic I/R injury and regulation of intrinsic pathway of apoptosis and autophagy. Methods. Three doses of ethyl pyruvate (20 mg/kg, 40 mg/kg, and 80 mg/kg) were administered 1 h before a model of segmental (70%) hepatic warm ischemia was established in Balb/c mice. All serum and liver tissues were obtained at three different time points (4 h, 8 h, and 16 h). Results. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and pathological features were significantly ameliorated by ethyl pyruvate (80 mg/kg). The expression of Bcl-2, Bax, Beclin-1, and LC3, which play an important role in the regulation of intrinsic pathway of apoptosis and autophagy, was also obviously decreased by ethyl pyruvate (80 mg/kg). Furthermore, ethyl pyruvate inhibited the HMGB1/TLR4/ NF-κb axis and the release of cytokines (TNF-α and IL-6). Conclusion. Our results showed that ethyl pyruvate might attenuate to hepatic I/R injury by inhibiting intrinsic pathway of apoptosis and autophagy, mediated partly through downregulation of HMGB1/TLR4/ NF-κb axis and the competitive interaction with Beclin-1 of HMGB1.
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19.6
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作者：
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通讯作者：
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