Division of Nephrology, Federal University of São Paulo (UNIFESP), Rua Botucatu 740, 04023-900 São Paulo, Brazil.
Division of Nephrology, University of Groningen, University Medical Centre Groningen (UMCG), P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
Nutrients. 2018 Sep 11;10(9):1283. doi: 10.3390/nu10091283.
Chronic kidney disease and inflammation promote loss of Klotho expression. Given the well-established anti-inflammatory effects of omega-3 fatty acids, we aimed to investigate the effect of fish oil supplementation in a model of CKD.
Male C57BL/6 mice received supplementation with an adenine-enriched diet (AD, = 5) or standard diet (CTL, = 5) for 10 days. Two other experimental groups were kept under the adenine diet for 10 days. Following adenine withdrawal on the 11th day, the animals returned to a standard diet supplemented with fish oil (Post AD-Fish oil, = 9) or not (Post AD-CTL, = 9) for an additional period of 7 days.
Adenine mice exhibited significantly higher mean serum urea, creatinine, and renal expression of the pro-inflammatory markers Interleukin-6 (IL-6), C-X-C motif chemokine 10 (CXCL10), and Interleukin-1β (IL-1β), in addition to prominent renal fibrosis and reduced renal Klotho gene expression compared to the control. Post AD-Fish oil animals demonstrated a significant reduction of IL-6, C-X-C motif chemokine 9 (CXCL9), and IL-1β compared to Post AD-CTL animals. However, serum creatinine, renal fibrosis, and Klotho were not significantly different in the fish oil-treated group. Furthermore, renal histomorphological changes such as tubular dilatation and interstitial infiltration persisted despite treatment.
Fish oil supplementation reduced renal pro-inflammatory markers but was not able to restore renal function nor Klotho expression in an adenine-induced CKD model.
慢性肾脏病和炎症会促进 Klotho 表达的丧失。鉴于 ω-3 脂肪酸具有明确的抗炎作用,我们旨在研究鱼油补充剂在 CKD 模型中的作用。
雄性 C57BL/6 小鼠接受富含腺嘌呤的饮食(AD,n=5)或标准饮食(CTL,n=5)补充 10 天。另外两个实验组继续接受腺嘌呤饮食 10 天。第 11 天停用腺嘌呤后,动物恢复标准饮食,并补充鱼油(Post AD-Fish oil,n=9)或不补充(Post AD-CTL,n=9),再持续 7 天。
与对照组相比,腺嘌呤组的小鼠血清尿素、肌酐和促炎标志物白细胞介素 6(IL-6)、C-X-C 基序趋化因子 10(CXCL10)和白细胞介素 1β(IL-1β)的肾脏表达明显升高,此外还表现出明显的肾脏纤维化和 Klotho 基因表达降低。与 Post AD-CTL 组相比,Post AD-Fish oil 组的 IL-6、C-X-C 基序趋化因子 9(CXCL9)和 IL-1β显著减少。然而,鱼油治疗组的血清肌酐、肾脏纤维化和 Klotho 没有显著差异。此外,尽管进行了治疗,但肾脏组织形态学变化(如肾小管扩张和间质浸润)仍然存在。
鱼油补充剂可降低肾脏促炎标志物,但不能恢复腺嘌呤诱导的 CKD 模型中的肾功能或 Klotho 表达。