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.

先前我们已经证明，抗坏血酸（AsA）缺乏会导致成骨性疾病Shioogi（ODS）大鼠的肝脏和肠道发生炎症性变化，而后者无法合成AsA。我们已经提出，AsA缺乏症会增加肠道白细胞介素（IL）-6的产生，并通过以下途径刺激肝脏急性期蛋白（APPs）的表达：门静脉。在这项研究中，我们确定了在无菌（GF）ODS大鼠中是否诱发了AsA缺乏引起的这些肝脏和肠道炎症变化。在18天中，在SPF条件下给雄性不含特定病原体（SPF）的ODS大鼠喂食含600 mg AsA / kg的基础饮食（对照组）或无AsA饮食（AsA缺乏组）的饮食，而雄性GF ODS大鼠在GF条件下接受基础饮食（对照组）或无AsA饮食（AsA缺乏组）。首先，AsA缺乏明显提高了SPF和GF大鼠APP的肝表达。在一些APP的肝mRNA水平中，观察到GF和AsA缺乏症作用之间的显着相互作用。其次，AsA缺乏会增加SPF和GF大鼠的肠道IL-6和IL-1βmRNA水平，在这些空肠和盲肠的mRNA水平中，观察到了GF和AsA缺乏效应之间的显着相互作用。在SPF和GF大鼠中，AsA缺乏会升高门静脉IL-6的浓度。这些结果表明，AsA缺乏会引起GF和SPF ODS大鼠的肝脏和肠道炎症变化，并表明AsA缺乏可以直接诱导肠道炎症变化，而没有肠道菌群的参与。