Acute Changes in Dietary ω-3 and ω-6 Polyunsaturated Fatty Acids Have a Pronounced Impact on Survival following Ischemic Renal Injury and Formation of Renoprotective Docosahexaenoic Acid-Derived Protectin D1
Acute Changes in Dietary ω-3 and ω-6 Polyunsaturated Fatty Acids Have a Pronounced Impact on Survival following Ischemic Renal Injury and Formation of Renoprotective Docosahexaenoic Acid-Derived Protectin D1
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DOI：
10.4049/jimmunol.0802064
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发表时间：
2009-03-01
影响因子：
4.4
通讯作者：
Gronert, Karsten
中科院分区：
文献类型：
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作者：
Hassan, Iram R.;Gronert, Karsten
炎症加重在缺血性肾损伤(IRI)的发病机制中起着重要作用，IRI是内源性急性肾功能衰竭的主要原因。临床研究表明，长期服用omega-3多不饱和脂肪酸(PUFA)可改善肾功能，降低死亡或终末期肾脏疾病的风险。二十二碳六烯酸是鱼油中一种主要的omega-3多不饱和脂肪酸，它在大多数人体组织中都存在，并被转化为保护素D1(PD1)，具有抗炎和促进分解的生物活性。我们利用所有已建立的小鼠模型和基于液-质联用/质谱学的脂类组学方法，研究了急性膳食调节omega-3或omega-6多不饱和脂肪酸对IRI和肾脏脂质海绵样环的影响。肾缺血30分钟后，w-6饮食组大鼠的血肌酐显著升高，而omega-3配对饮食组的肾功能保持正常。值得注意的是，将缺血延长到45分钟，omega-6组的死亡率为100%，而omega-3组的死亡率为0%。Omega-3组对IRI的保护与减少多形核白细胞募集、趋化因子和细胞因子水平、阻止脂氧合酶和环氧合酶衍生二十烷类化合物的形成以及PD1全身治疗PD1的肾脏水平增加有关，PD1全身治疗减少了肾脏多形核白细胞的流入，更重要的是，在受损和未受损的肾脏中，放大了肾脏保护性血红素加氧酶-1蛋白和mRNA的表达。这些发现表明，治疗或饮食对PDI回路的放大可以抑制急性肾脏损伤，饮食中omega-3和omega-6多不饱和脂肪酸的短期变化显著影响肾脏脂质类海绵样蛋白的形成和结局或IRI。免疫学杂志，2009,182：3223-3232。
Exacerbated inflammation plays an important role in the pathogenesis of ischemic renal injury (IRI), which is the major cause of intrinsic acute renal failure. Clinical studies suggest that long-term treatment with omega-3 polyunsaturated fatty acids (PUFA) improves renal function and lowers the risk of death or end-stage renal disease. Docosahexaenoic acid, a principle omega-3 PUFA of fish oils, is of particular interest as it is found in most human tissues and is converted to protectin D1 (PD1), which exhibits antiinflammatory and proresolving bioactions. We set out to investigate the impact of acute dietary modulation of omega-3 or omega-6 PUFA on IRI and renal lipid autacoid circuits, using all established mouse model and liquid chromatography-mass spectroscopy/mass spectroscopy-based lipidomics. Thirty minutes of renal ischemia significantly elevated serum creatinine in the w-6 diet group while renal function remained normal in the matched omega-3 diet group. Notably, extending ischemia to 45 min caused 100% mortality in the omega-6 group, in sharp contrast to 0% mortality in the omega-3 group. Protection against IRI in the omega-3 group correlated with decreased polymorphonuclear leukocyte recruitment, chemokine and cytokine levels, abrogated formation of lipoxygenase-and cyclooxygenase-derived eicosanoids, and increased renal levels of PD1 Systemic treatment with PD1 reduced kidney polymorphonuclear leukocyte influx and, more importantly, amplified renoprotective heme-oxygenase-1 protein and mRNA expression In injured and uninjured kidneys. These findings suggest therapeutic or dietary amplification of PDI circuits restrains acute renal injury and that short-term changes in dietary omega-3 and omega-6 PUFA dramatically impacts renal lipid autacoid formation and outcome or IRI. The Journal of Immunology, 2009, 182: 3223-3232.