BACKGROUND Acute kidney injury (AKI) is an important complication after major surgery and solid organ transplantation. Here, we present a dietary omega-3 polyunsaturated fatty acid (n3-PUFA) supplementation study to investigate whether pre-treatment can reduce ischemia induced AKI in mice. METHODS Male 12-14 week old C57BL/6 J mice received a linoleic acid rich sunflower oil based standard diet containing 10 % fat (STD) or the same diet enriched with n3-PUFA (containing 1 % EPA and 1 % DHA) (STD + n3). After 14 days of feeding bilateral 30 min renal ischemia reperfusion injury (IRI) was conducted to induce AKI and mice were sacrificed at 24 h. Serum creatinine and blood urea nitrogen (BUN) as well as liver enzyme elevation were measured. Kidney damage was analyzed by histology and immunohistochemistry. Furthermore, pro-inflammatory cytokines (IL-6, MCP-1) were determined by qPCR. FA and oxylipin pattern were quantified in blood and kidneys by GC-FID and LC-MS/MS, respectively. RESULTS n3-PUFA supplementation prior to renal IRI increased systemic and renal levels of n3-PUFA. Consistently, eicosanoids and other oxylipins derived from n3-PUFA including precursors of specialized pro-resolving mediators were elevated while n6-PUFA derived mediators such as pro-inflammatory prostaglandins were decreased. Feeding of n3-PUFA did not attenuate renal function impairment, morphological renal damage and inflammation characterized by IL-6 and MCP-1 elevation or neutrophil infiltration. However, the tubular transport marker alpha-1 microglobulin (A1M) was significantly higher expressed in proximal tubular epithelial cells of STD + n3 compared to STD fed mice. This indicates a better integrity of proximal tubular epithelial cells and thus significant protection of tubular function. In addition, heme oxygenase-1 (HO-1) which protects tubular function was also up-regulated in the treatment group receiving n3-PUFA supplemented chow. DISCUSSION We showed that n3-PUFA pre-treatment did not affect overall renal function or renal inflammation in a mouse model of moderate ischemia induced AKI, but tubular transport was improved. In conclusion, dietary n3-PUFA supplementation altered the oxylipin levels significantly but did not protect from renal function deterioration or attenuate ischemia induced renal inflammation.

中文翻译：

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日粮omega-3 PUFA改善了缺血引起的小鼠急性肾损伤后的肾小管功能，但并未减弱肾功能的损害。

背景技术急性肾损伤（AKI）是大手术和实体器官移植后的重要并发症。在这里，我们目前进行饮食中的omega-3多不饱和脂肪酸（n3-PUFA）补充研究，以研究预处理是否可以减少小鼠缺血性诱导的AKI。方法12-14周龄的雄性C57BL / 6 J小鼠接受富含亚油酸的葵花籽油为基础的日粮，其中含有10％的脂肪（STD）或富含n3-PUFA（含有1％的EPA和1％的DHA）的相同饮食（STD） + n3）。喂食14天后，进行双侧30分钟肾缺血再灌注损伤（IRI）诱导AKI，并在24 h处死小鼠。测量血清肌酐和血尿素氮（BUN）以及肝酶升高。通过组织学和免疫组织化学分析肾脏损害。此外，通过qPCR确定促炎细胞因子（IL-6，MCP-1）。通过GC-FID和LC-MS / MS分别定量血液和肾脏中的FA和脂蛋白模式。结果在肾脏IRI之前补充n3-PUFA会增加n3-PUFA的全身和肾脏水平。一致地，衍生自n3-PUFA的类花生酸和其他脂蛋白（包括专门的促分解介体的前体）升高，而衍生自n6-PUFA的促炎性前列腺素等介体则减少。饲喂n3-PUFA不会减轻肾功能损害，肾脏形态损害和以IL-6和MCP-1升高或中性粒细胞浸润为特征的炎症。但是，与STD喂养的小鼠相比，STD + n3的近端肾小管上皮细胞中的肾小管转运标记物α-1微球蛋白（A1M）的表达明显更高。这表明近端肾小管上皮细胞具有更好的完整性，从而显着保护了肾小管功能。此外，在接受n3-PUFA补充食物的治疗组中，保护肾小管功能的血红素加氧酶-1（HO-1）也被上调。讨论我们显示，在中度缺血诱导的AKI小鼠模型中，n3-PUFA预处理不影响总体肾功能或肾脏炎症，但肾小管转运得到改善。总之，饮食中添加n3-PUFA可以显着改变脂蛋白的水平，但不能保护肾脏功能不致恶化或减轻局部缺血引起的肾脏炎症。在接受n3-PUFA补充食物的治疗组中，保护肾小管功能的血红素加氧酶-1（HO-1）也被上调。讨论我们显示，在中度缺血诱导的AKI小鼠模型中，n3-PUFA预处理不影响总体肾功能或肾脏炎症，但肾小管转运得到改善。总之，饮食中添加n3-PUFA可以显着改变脂蛋白的水平，但不能保护肾脏功能不致恶化或减轻局部缺血引起的肾脏炎症。在接受n3-PUFA补充食物的治疗组中，保护肾小管功能的血红素加氧酶-1（HO-1）也被上调。讨论我们显示，在中度缺血诱导的AKI小鼠模型中，n3-PUFA预处理不影响总体肾功能或肾脏炎症，但肾小管转运得到改善。总之，饮食中添加n3-PUFA可以显着改变脂蛋白的水平，但不能保护肾脏功能不致恶化或减轻缺血引起的肾脏炎症。