Barden Anne E, Shinde Sujata, Burke Valerie, Puddey Ian B, Beilin Lawrence J, Irish Ashley B, Watts Gerald F, Mori Trevor A
Medical School, University of Western Australia, Australia.
Medical School, University of Western Australia, Australia.
Prostaglandins Other Lipid Mediat. 2018 May;136:1-8. doi: 10.1016/j.prostaglandins.2018.03.002. Epub 2018 Mar 22.
Neutrophils release leukotriene (LT)B and myeloperoxidase (MPO) that may be important mediators of chronic inflammation in chronic kidney disease (CKD). The n-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have the potential to attenuate inflammation through production of LTB and the Specialized Proresolving Lipid Mediators (SPM) that promote the resolution of inflammation. In animal models, coenzyme Q10 (CoQ) also attenuates inflammation by reducing MPO and LTB.
This study evaluated the independent and combined effects of n-3 FA and CoQ supplementation on neutrophil leukotrienes, the pro-inflammatory eicosanoid 5-hydroxyeicosatetraenoic acid (5-HETE), SPM, and plasma MPO, in patients with CKD.
In a double-blind, placebo-controlled intervention of factorial design, 85 patients with CKD were randomized to either n-3 FA (4 g), CoQ (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. Plasma MPO and calcium ionophore-stimulated neutrophil release of LTs, 5-HETE and SPM were measured at baseline and after 8 weeks.
Seventy four patients completed the intervention. n-3 FA, but not CoQ, significantly increased neutrophil LTB (P < 0.0001) and the SPM 18-hydroxyeicosapentaenoic acid (18-HEPE), resolvin E1 (RvE1), resolvin E2 (RvE2) and resolvin E3 (RvE3) that derive from EPA, as well as 17-hydroxydocosahexaenoic acid (17-HDHA) and resolvin D5 (RvD5) that derive from DHA (all P < 0.01). Neutrophil LTB4 and its metabolites, and 5-HETE were not significantly altered by n-3 FA or CoQ. Plasma MPO was significantly reduced with n-3 FA alone (P = 0.013) but not when given in combination with CoQ.
n-3 FA supplementation in patients with CKD leads to increased neutrophil release of LTB and several SPM, as well as a reduction in plasma MPO that may have important implications for limiting chronic inflammation.
中性粒细胞释放白三烯（LT）B和髓过氧化物酶（MPO），它们可能是慢性肾脏病（CKD）慢性炎症的重要介质。n-3脂肪酸（n-3 FA）二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）有可能通过产生LTB和促进炎症消退的特殊促消退脂质介质（SPM）来减轻炎症。在动物模型中，辅酶Q10（CoQ）也通过降低MPO和LTB来减轻炎症。
本研究评估了补充n-3 FA和CoQ对CKD患者中性粒细胞白三烯、促炎类花生酸类物质5-羟基二十碳四烯酸（5-HETE）、SPM和血浆MPO的独立及联合作用。
在一项双盲、安慰剂对照的析因设计干预研究中，85例CKD患者被随机分为每日服用n-3 FA（4 g）、CoQ（200 mg）、两种补充剂或对照（4 g橄榄油），共8周。在基线和8周后测量血浆MPO以及钙离子载体刺激的中性粒细胞释放的LTs、5-HETE和SPM。
74例患者完成了干预。n-3 FA而非CoQ显著增加了中性粒细胞LTB（P<0.0001）以及源自EPA的SPM 18-羟基二十碳五烯酸（18-HEPE）、消退素E1（RvE1）、消退素E2（RvE2）和消退素E3（RvE3），以及源自DHA的17-羟基二十二碳六烯酸（17-HDHA）和消退素D5（RvD5）（所有P<0.01）。n-3 FA或CoQ对中性粒细胞LTB4及其代谢产物以及5-HETE无显著影响。单独使用n-3 FA可显著降低血浆MPO（P=0.013），但与CoQ联合使用时则无此效果。
CKD患者补充n-3 FA可导致中性粒细胞释放的LTB和几种SPM增加，以及血浆MPO降低，这可能对限制慢性炎症具有重要意义。
