澳大利亚随机对照研究发现n-3脂肪酸可促进慢性肾病炎症消退
炎症启动（initiation）、发展之后的消退（resolution）是受到体内促消退介质（proresolving mediator）调控的主动过程。继发现由花生四烯酸衍生的脂氧素（lipoxin）后，新近又从炎症消退阶段的炎性渗出物中分离出由ω-3多不饱和脂肪酸转化而来的消退素（resolvin）与保护素（protectin），它们也具有强效的抗炎促消退效应，成为促炎症消退介质的新成员。目前发现的消退素主要包含10种，根据来源ω-3多不饱和脂肪酸的不同，消退素可分为E类和D类。前者来源于二十碳五烯酸（EPA），称E类消退素（RvE）；而后者来源于二十二碳六烯酸（DHA），称为D类消退素（RvD）。。
2016年4月，欧洲肠外肠内营养学会（ESPEN）官方期刊《临床营养》正式发表了西澳大利亚大学医学与药学学院、特雷森儿童研究所、皇家珀斯医院的随机双盲安慰剂对照研究，发现慢性肾病（CKD）患者补充n-3脂肪酸8周后血浆特异性促消退脂类介质（SPM）显著增加，这可能对限制CKD持续轻度炎症具有重要意义。
在该研究中，85例患者随机接受n-3脂肪酸（4g）、辅酶Q10（200mg）、二者或橄榄油（4g）干预共8周，并在干预前后用液相色谱-串联质谱法检测血浆SPM：18-羟二十碳五烯酸（18-HEPE）、17-羟二十二碳六烯酸（17-HDHA）、RvD1、17R-RvD1和RvD2）。
结果74例患者完成了8周干预。n-3脂肪酸组与辅酶Q10组相比，18-HEPE和17-HDHA（分别为E类和D类消退素上游前体）的血浆水平显著增加（P＜0.0001）。n-3脂肪酸干预后，RvD1显著增加（P=0.036），其他SPM未见变化。回归分析提示血小板EPA和DHA变化可分别预测n-3脂肪酸干预后18-HEPE和17-HDHA的增加。
Clin Nutr. 2016 Apr;35(2):331-6.
A randomized controlled trial of the effects of n-3 fatty acids on resolvins in chronic kidney disease.
Mas E, Barden A, Burke V, Beilin LJ, Watts GF, Huang RC, Puddey IB, Irish AB, Mori TA.
School of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia, Australia.
Telethon Kid's Institute, Australia.
Department of Nephrology and Transplantation, Royal Perth Hospital, Perth, WA 6000, Australia.
BACKGROUND AND OBJECTIVE: The high incidence of cardiovascular disease (CVD) in chronic kidney disease (CKD) is related partially to chronic inflammation. n-3 Fatty acids have been shown to have anti-inflammatory effects and to reduce the risk of CVD. Specialized Proresolving Lipid Mediators (SPMs) derived from the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) actively promote the resolution of inflammation. This study evaluates the effects of n-3 fatty acid supplementation on plasma SPMs in patients with CKD.
METHODS: In a double-blind, placebo-controlled intervention of factorial design, 85 patients were randomized to either n-3 fatty acids (4 g), Coenzyme Q10 (CoQ) (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. The SPMs 18-HEPE, 17-HDHA, RvD1, 17R-RvD1, and RvD2, were measured in plasma by liquid chromatography-tandem mass spectrometry before and after intervention.
RESULTS: Seventy four patients completed the 8 weeks intervention. n-3 Fatty acids but not CoQ significantly increased (P < 0.0001) plasma levels of 18-HEPE and 17-HDHA, the upstream precursors to the E- and D-series resolvins, respectively. RvD1 was significantly increased (P = 0.036) after n-3 fatty acids, but no change was seen in other SPMs. In regression analysis the increase in 18-HEPE and 17-HDHA after n-3 fatty acids was significantly predicted by the change in platelet EPA and DHA, respectively.
CONCLUSION: SPMs are increased after 8 weeks n-3 fatty acid supplementation in patients with CKD. This may have important implications for limiting ongoing low grade inflammation in CKD.
PMID: 25908532
DOI: 10.1016/j.clnu.2015.04.004
