Department of Animal Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
Laboratory of Grassland and Animal Feed Production, Graduate School of Bioresources, Mie University, Tsu 514-8507, Japan.
J Nutr Biochem. 2020 Dec;86:108485. doi: 10.1016/j.jnutbio.2020.108485. Epub 2020 Aug 20.
We have previously demonstrated that ascorbic acid (AsA) deficiency causes inflammatory changes in the liver and intestine in Osteogenic Disorder Shionogi (ODS) rats, which are unable to synthesize AsA. We have suggested that AsA deficiency increased intestinal interleukine (IL)-6 production, stimulating hepatic acute phase proteins (APPs) expression via the portal vein. In this study, we determined whether these hepatic and intestinal inflammatory changes by AsA deficiency are induced in germ-free (GF) ODS rats. For 18 days, male specific pathogen-free (SPF) ODS rats were fed the basal diet containing 600 mg AsA/kg (control group) or the AsA-free diet (AsA-deficient group) in SPF conditions, while male GF ODS rats were fed the basal diet (control group) or the AsA-free diet (AsA-deficient group) in GF conditions. Firstly, AsA deficiency significantly elevated the hepatic expression of APPs in both SPF and GF rats. In hepatic mRNA levels of some APPs, significant interaction between GF and AsA-deficiency effects was observed. Secondly, AsA deficiency elevated intestinal IL-6 and IL-1β mRNA levels in both SPF and GF rats, and significant interaction between GF and AsA-deficiency effects was observed in these mRNA levels of jejunum and cecum. In SPF and GF rats, AsA deficiency elevated portal IL-6 concentration. These results show that AsA deficiency caused hepatic and intestinal inflammatory changes in both the GF and SPF ODS rats and indicate that AsA deficiency could directly induce intestinal inflammatory changes without the involvement of gut microbiota.
我们之前已经证明，在无法合成抗坏血酸（AsA）的成骨障碍 Shionogi（ODS）大鼠中，AsA 缺乏会导致肝脏和肠道发生炎症变化。我们认为，AsA 缺乏会增加肠道白细胞介素（IL）-6 的产生，通过门静脉刺激肝脏急性期蛋白（APP）的表达。在这项研究中，我们确定了无特定病原体（GF）ODS 大鼠中是否存在由 AsA 缺乏引起的这些肝和肠炎症变化。在 18 天的时间里，雄性无菌（GF）ODS 大鼠在 SPF 条件下分别喂食含有 600mg AsA/kg 的基础饮食（对照组）或不含 AsA 的饮食（AsA 缺乏组），而雄性 GF ODS 大鼠则在 GF 条件下喂食基础饮食（对照组）或不含 AsA 的饮食（AsA 缺乏组）。首先，AsA 缺乏显著提高了 SPF 和 GF 大鼠肝脏中 APP 的表达。在一些 APP 的肝 mRNA 水平上，观察到 GF 和 AsA 缺乏效应之间存在显著的相互作用。其次，AsA 缺乏提高了 SPF 和 GF 大鼠肠道中 IL-6 和 IL-1β 的 mRNA 水平，并且在这些空肠和盲肠的 mRNA 水平上观察到了 GF 和 AsA 缺乏效应之间的显著相互作用。在 SPF 和 GF 大鼠中，AsA 缺乏增加了门静脉 IL-6 浓度。这些结果表明，AsA 缺乏在 GF 和 SPF ODS 大鼠中引起了肝和肠的炎症变化，并且表明 AsA 缺乏可以直接引起肠道炎症变化，而无需肠道微生物群的参与。
