Wang Peng-Fei, Yao Dan-Hua, Hu Yue-Yu, Li Yousheng
Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
Department of Neurology, The Fourth Affiliated Hospital of Tongji University, Shanghai 200081, China.
Biomol Ther (Seoul). 2019 Mar 1;27(2):222-230. doi: 10.4062/biomolther.2018.052.
Intestinal barrier dysfunction always accompanies cirrhosis in patients with advanced liver disease and is an important contributor facilitating bacterial translocation (BT), which has been involved in the pathogenesis of cirrhosis and its complications. Several studies have demonstrated the protective effect of Vitamin D on intestinal barrier function. However, severe cholestasis leads to vitamin D depletion. This study was designed to test whether vitamin D therapy improves intestinal dysfunction in cirrhosis. Rats were subcutaneously injected with 50% sterile CCl (a mixture of pure CCl and olive oil, 0.3 mL/100 g) twice a week for 6 weeks. Next, 1,25(OH)D (0.5 μg/100 g) and the vehicle were administered simultaneously with CCl to compare the extent of intestinal histologic damage, tight junction protein expression, intestinal barrier function, BT, intestinal proliferation, apoptosis, and enterocyte turnover. Intestinal heme oxygenase-1 (HO-1) expression and oxidative stress were also assessed. We found that vitamin D could maintain intestinal epithelial proliferation and turnover, inhibit intestinal epithelial apoptosis, alleviate structural damage, and prevent BT and intestinal barrier dysfunction. These were achieved partly through restoration of HO-1 and inhibition of oxidative stress. Taken together, our results suggest that vitamin D ameliorated intestinal epithelial turnover and improved the integrity and function of intestinal barrier in CCl-induced liver cirrhotic rats. HO-1 signaling activation was involved in these above beneficial effects.
肠道屏障功能障碍在晚期肝病患者的肝硬化过程中始终存在，并且是促进细菌移位（BT）的重要因素，而细菌移位已参与肝硬化及其并发症的发病机制。多项研究已证实维生素D对肠道屏障功能具有保护作用。然而，严重胆汁淤积会导致维生素D缺乏。本研究旨在测试维生素D治疗是否能改善肝硬化患者的肠道功能障碍。大鼠每周皮下注射两次50%无菌CCl4（纯CCl4与橄榄油的混合物，0.3 mL/100 g），持续6周。接下来，将1,25(OH)D（0.5 μg/100 g）和赋形剂与CCl4同时给药，以比较肠道组织学损伤程度、紧密连接蛋白表达、肠道屏障功能、细菌移位、肠道增殖、细胞凋亡和肠上皮细胞更新情况。还评估了肠道血红素加氧酶-1（HO-1）表达和氧化应激。我们发现维生素D可以维持肠上皮细胞增殖和更新，抑制肠上皮细胞凋亡，减轻结构损伤，并预防细菌移位和肠道屏障功能障碍。这些作用部分是通过恢复HO-1和抑制氧化应激来实现的。综上所述，我们的结果表明维生素D改善了CCl4诱导的肝硬化大鼠的肠上皮细胞更新，并改善了肠道屏障的完整性和功能。HO-1信号激活参与了上述有益作用。
