Mitochondrial dysfunction in rat splenocytes following hemorrhagic shock.
Mitochondrial dysfunction in rat splenocytes following hemorrhagic shock.
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DOI：
10.1016/j.bbadis.2017.08.024
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Raju R
中科院分区：
文献类型：
--
作者：
Warren M;Subramani K;Schwartz R;Raju R
线粒体功能的调节在失血性休克后的细胞内稳态中是至关重要的。失血性休克导致体液流失以及组织氧气和营养物质的可用性降低。脾脏是一种次级淋巴器官，在“过滤血液”以及先天性和适应性免疫反应中发挥关键作用。为了了解失血性休克的分子基础，我们研究了脾细胞线粒体呼吸的变化，以及伴随的免疫和代谢改变。在我们的大鼠模型中，通过放血60%的总血容量，然后用乳酸林格氏液复苏来诱导出血性损伤（HI）。另一组动物出血，但未接受液体复苏。用Seahorse分析仪测定脾细胞的耗氧率。我们发现一个显着降低耗氧率在脾细胞HI相比，假手术大鼠。线粒体应激试验显示基础耗氧率、ATP生成、最大呼吸和备用呼吸量降低。线粒体膜电位，柠檬酸合酶活性，也降低了脾细胞HI后。脾细胞中的低氧应答通过增加的Hif 1 α基因表达来证实。HI后脾细胞线粒体应激蛋白、热休克蛋白60水平升高，高迁移率族蛋白1（HMGB 1）表达增加。通过IL-6、IFN-β、Mip-1α、IL-10和NFκ bp 65的表达显著增加证明炎症反应增加。总之，我们得出结论，脾细胞氧化磷酸化和代谢严重受损后HI。
The regulation of mitochondrial function is critical in cellular homeostasis following hemorrhagic shock. Hemorrhagic shock leads to fluid loss and reduced availability of oxygen and nutrients to tissues. The spleen is a secondary lymphoid organ playing a key role in ‘filtering the blood’ and in the innate and adaptive immune responses. To understand the molecular basis of hemorrhagic shock, we investigated the changes in splenocyte mitochondrial respiration, and concomitant immune and metabolic alterations. The hemorrhagic injury (HI) in our rat model was induced by bleeding 60% of the total blood volume followed by resuscitation with Ringers lactate. Another group of animals was subjected to hemorrhage, but did not receive fluid resuscitation. Oxygen consumption rate of splenocytes were determined using a Seahorse analyzer. We found a significantly reduced oxygen consumption rate in splenocytes following HI compared to sham operated rats. The mitochondrial stress test revealed a decreased basal oxygen consumption rate, ATP production, maximal respiration and spare respiratory capacity. The mitochondrial membrane potential, and citrate synthase activity, were also reduced in the splenocytes following HI. Hypoxic response in the splenocyte was confirmed by increased gene expression of Hif1α. Elevated level of mitochondrial stress protein, hsp60 and induction of high mobility group box1 protein (HMGB1) were observed in splenocytes following HI. An increased inflammatory response was demonstrated by significantly increased expression of IL-6, IFN-β, Mip-1α, IL-10 and NFκbp65. In summary, we conclude that splenocyte oxidative phosphorylation and metabolism were severely compromised following HI.
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影响因子：
6.2
作者：
Laird MD;Shields JS;Sukumari-Ramesh S;Kimbler DE;Fessler RD;Shakir B;Youssef P;Yanasak N;Vender JR;Dhandapani KM
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