The role of mesenteric lymph exosomal lipid mediators following intestinal ischemia-reperfusion injury on activation of inflammation
The role of mesenteric lymph exosomal lipid mediators following intestinal ischemia-reperfusion injury on activation of inflammation
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DOI：
10.1097/ta.0000000000002897
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发表时间：
2020-12-01
影响因子：
3.4
通讯作者：
Otomo, Yasuhiro
中科院分区：
文献类型：
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作者：
Senda, Atsushi;Morishita, Koji;Otomo, Yasuhiro
研究背景出血性休克引起的肠缺血可诱导全身炎症反应。先前的研究表明，肠系膜淋巴（ML）在肠道介导的炎症中起着至关重要的作用。脂质介质，如溶血磷脂酰胆碱（LPC），其中含有多不饱和脂肪酸（PUFA），存在于休克后ML。外泌体也存在于ML中，并作为脂质的跨细胞载体;然而，它们在休克后全身性炎症中的作用尚未揭示。在这里，我们的目的是确定肠缺血后ML外泌体中脂质介质的变化。方法雄性Sprague-Dawley大鼠行腹腔镜手术，然后行ML导管插管。通过上级肠系膜动脉夹闭使动物经受60分钟的肠缺血，随后再灌注120分钟。在肠缺血前后获得肠系膜淋巴液，并通过超离心从ML中分离外泌体。使用单核细胞核因子κ B（NF-κ B）活化测定法测定ML外泌体的生物活性。提取ML外泌体的脂质并通过液相色谱/电喷雾电离质谱进行定量。肠缺血后肠系膜淋巴外泌体诱导的NF-κ B活化显著增加，脂质分析显示含PUFA的LPC浓度显著增加。此外，含PUFA的LPC也诱导NF-κ B活化。结论ML外泌体中具有生物活性的脂质介质可能参与肠缺血后的炎症反应。
BACKGROUNDIntestinal ischemia caused by hemorrhagic shock is known to induce systemic inflammatory responses. Previous studies have shown that mesenteric lymph (ML) plays a crucial role in gut-mediated inflammation. Lipid mediators, such as lysophosphatidylcholines (LPCs), which contain polyunsaturated fatty acids (PUFAs), are present in the postshock ML. Exosomes are also present in the ML and act as transcellular carriers of lipids; however, their role in postshock systemic inflammation has not been revealed. Here, we aimed to identify changes in lipid mediators in ML exosomes after intestinal ischemia. METHODSMale Sprague-Dawley rats underwent laparotomy, followed by ML duct cannulation. Animals were subjected to 60 minutes of intestinal ischemia by superior mesenteric artery clamping, followed by 120 minutes of reperfusion. Mesenteric lymph was obtained before and after intestinal ischemia, and exosomes were isolated from ML by ultracentrifugation. The biological activity of ML exosomes was determined using the monocyte nuclear factor kappa B (NF-kappa B) activation assay. Lipids of ML exosomes were extracted and quantified by liquid chromatography/electrospray ionization mass spectrometry. RESULTSMesenteric lymph exosome-induced NF-kappa B activation significantly increased after intestinal ischemia, and lipid analysis revealed a significant increase in the concentration of PUFA-containing LPCs. In addition, PUFA-containing LPCs also induced NF-kappa B activation. CONCLUSIONOur results suggest that biologically active lipid mediators in ML exosomes may be involved in the inflammatory response after intestinal ischemia.