肠缺血再灌注损伤后肠系膜淋巴 exosomal 脂质介质在炎症激活中的作用。
The role of mesenteric lymph exosomal lipid mediators following intestinal ischemia-reperfusion injury on activation of inflammation.
机构信息
From the Department of Acute Critical Care and Disaster Medicine (A.S., M.Y., Y.O.), Graduate School of Medical and Dental Sciences, and Department of Acute Critical Care and Disaster Medicine (K.M., B.T., J.A., Y.O.), Hospital of Medicine, Tokyo Medical and Dental University, Tokyo, Japan; Emergency and Critical Care Center (M.K.), Tokyo Women's Medical University Medical Center East; Department of Biological Sciences (S.D., A.W., T.K.), Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan; and Department of Surgery (R.C.), Riverside University Health System Medical Center, Loma Linda University School of Medicine, Loma Linda, California.
出版信息
J Trauma Acute Care Surg. 2020 Dec;89(6):1099-1106. doi: 10.1097/TA.0000000000002897.
BACKGROUND
Intestinal 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.
METHODS
Male 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 κB (NF-κB) activation assay. Lipids of ML exosomes were extracted and quantified by liquid chromatography/electrospray ionization mass spectrometry.
RESULTS
Mesenteric lymph exosome-induced NF-κB 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-κB activation.
CONCLUSION
Our results suggest that biologically active lipid mediators in ML exosomes may be involved in the inflammatory response after intestinal ischemia.
背景
已知出血性休克引起的肠缺血会引发全身炎症反应。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。含有多不饱和脂肪酸（PUFA）的脂类介质，如溶血磷脂酰胆碱（LPC），存在于休克后 ML 中。外泌体也存在于 ML 中，作为脂质的细胞间载体；然而，它们在休克后全身炎症中的作用尚未被揭示。在这里，我们旨在确定肠缺血后 ML 外泌体中脂质介质的变化。
方法
雄性 Sprague-Dawley 大鼠行剖腹术，然后行 ML 导管插管。动物通过夹闭肠系膜上动脉经历 60 分钟的肠缺血，然后再进行 120 分钟的再灌注。在肠缺血前后获取肠系膜淋巴，并通过超速离心从 ML 中分离出外泌体。使用单核细胞核因子 κB（NF-κB）激活测定法测定 ML 外泌体的生物活性。通过液相色谱/电喷雾电离质谱法提取和定量 ML 外泌体中的脂质。
结果
肠缺血后，肠系膜淋巴外泌体诱导的 NF-κB 激活显著增加，脂质分析显示含 PUFA 的 LPC 浓度显著增加。此外，含 PUFA 的 LPC 也诱导了 NF-κB 激活。
结论
我们的结果表明，ML 外泌体中的生物活性脂质介质可能参与了肠缺血后的炎症反应。
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