背景:α-酮戊二酸(AKG)在减轻炎症和增强肠道健康中起关键作用。
目的:本研究旨在探讨AKG是否可以通过减轻线粒体相关内质网膜的紊乱来对抗脂多糖(LPS)诱导的肠损伤。线粒体动力学功能失调,仔猪模型中的内质网应激。
方法:对24只仔猪进行2×2因子设计,饮食因素(基础饮食或1%AKG饮食)和LPS治疗(LPS或生理盐水)。在食用基础饮食或AKG饮食21天后,仔猪接受LPS或生理盐水注射。实验分为四个治疗组(对照组,基础饮食+生理盐水;LPS组,基础日粮+LPS;AKG组,AKG饮食+生理盐水;AKG_LPS组,AKG+LPS),每头由六只小猪组成。
结果:结果表明,与对照组相比,AKG增强空肠形态,抗氧化能力,以及紧密连接蛋白的mRNA和蛋白表达。此外,显示仔猪血清二胺氧化酶活性和D-乳酸含量降低。此外,AKG反映了内质网-线粒体系统的疾病较少,如AKG调节线粒体动力学关键分子的表达(线粒体钙单转体,视神经萎缩1、裂变1和动力蛋白相关蛋白1),内质网应激(激活转录因子4,激活转录因子6,C/EBP同源蛋白,真核起始因子2α,葡萄糖调节蛋白78,蛋白激酶R样内质网激酶),和线粒体相关的内质网膜(mitofusin-1,mitofusin-2,葡萄糖调节蛋白75和电压依赖性阴离子通道-1)。
结论:饮食AKG可以预防线粒体动力学功能障碍,内质网应激,和线粒体相关的内质网膜紊乱,最终缓解LPS诱导的仔猪肠道损伤。
BACKGROUND: α-Ketoglutarate (AKG) plays a pivotal role in mitigating inflammation and enhancing intestinal health.
OBJECTIVE: This study aimed to investigate whether AKG could protect against lipopolysaccharide (LPS)-induced intestinal injury by alleviating disorders in mitochondria-associated endoplasmic reticulum (MAM) membranes, dysfunctional mitochondrial dynamics, and endoplasmic reticulum (ER) stress in a piglet model.
METHODS: Twenty-four piglets were subjected to a 2 × 2 factorial design with dietary factors (basal diet or 1% AKG diet) and LPS treatment (LPS or saline). After 21 d of consuming either the basal diet or AKG diet, piglets received injections of LPS or saline. The experiment was divided into 4 treatment groups [control (CON) group: basal diet + saline; LPS group: basal diet +LPS; AKG group: AKG diet + saline; and AKG_LPS group: AKG + LPS], each consisting of 6 piglets.
RESULTS: The results demonstrated that compared with the CON group, AKG enhanced jejunal morphology, antioxidant capacity, and the messenger RNA and protein expression of tight junction proteins. Moreover, it has shown a reduction in serum diamine oxidase activity and D-lactic acid content in piglets. In addition, fewer disorders in the ER-mitochondrial system were reflected by AKG, as evidenced by AKG regulating the expression of key molecules of mitochondrial dynamics (mitochondrial calcium uniporter, optic atrophy 1, fission 1, and dynamin-related protein 1), ER stress [activating transcription factor (ATF) 4, ATF 6, CCAAT/enhancer binding protein homologous protein, eukaryotic initiation factor 2α, glucose-regulated protein (GRP) 78, and protein kinase R-like ER kinase], and MAM membranes [mitofusin (Mfn)-1, Mfn-2, GRP 75, and voltage-dependent anion channel-1].
CONCLUSIONS: Dietary AKG can prevent mitochondrial dynamic dysfunction, ER stress, and MAM membrane disorder, ultimately alleviating LPS-induced intestinal damage in piglets.