Wang Huihui, Gong Weiyi, Gao Jingxin, Cheng Wenxiu, Hu Yongdi, Hu Chunqiu
Department of Nutrition and Hygiene, School of Public Health, Anhui Medical University, Hefei, 230032, China; Women's Group Insurance Department, Lianyungang Maternal and Child Health Hospital, Lianyungang, 222000, China.
Department of Nutrition and Hygiene, School of Public Health, Anhui Medical University, Hefei, 230032, China.
Free Radic Biol Med. 2024 Nov 1;224:220-231. doi: 10.1016/j.freeradbiomed.2024.08.037. Epub 2024 Aug 28.
Vitamin D deficiency (VDD) has been found among alcoholics. However, little is known about the effect of VDD on alcoholic liver disease and the molecular mechanisms remain unclear. The aim of the current study was to evaluate whether vitamin D was deficient among patients with alcoholic fatty liver disease (AFLD) and the effect of VDD on chronic alcoholic liver injury and possible molecular mechanisms in mice. Our results found that lower 25-hydroxyvitamin D [25(OH)D] concentrations in patients with AFLD. And further analysis found that 25(OH)D is a protective factor in patients with AFLD. Mice experiments indicated that VDD can alter the composition of gut microbiota, down-regulate the protein levels of intestinal tight junction protein Occludin and E-cadherin, up-regulate the expression of inflammatory cytokines (tnf-α, il-1β, il-6, il-8, ccl2, il-10) in liver and colon tissue. And further exacerbated the protein levels of p65,P-IκB,P-p65 in alcoholic liver injury mice. In conclusion, VDD aggravates chronic alcoholic liver injury by activating NF-κB signaling pathway.
在酗酒者中发现了维生素D缺乏(VDD)。然而,关于VDD对酒精性肝病的影响知之甚少,其分子机制仍不清楚。本研究的目的是评估酒精性脂肪性肝病(AFLD)患者中是否存在维生素D缺乏,以及VDD对小鼠慢性酒精性肝损伤的影响及其可能的分子机制。我们的结果发现,AFLD患者的25-羟基维生素D[25(OH)D]浓度较低。进一步分析发现,25(OH)D是AFLD患者的一个保护因素。小鼠实验表明,VDD可改变肠道微生物群的组成,下调肠道紧密连接蛋白Occludin和E-钙黏蛋白的蛋白水平,上调肝脏和结肠组织中炎性细胞因子(肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6、白细胞介素-8、趋化因子配体2、白细胞介素-10)的表达。并进一步加剧酒精性肝损伤小鼠中p65、磷酸化核因子-κB抑制蛋白激酶、磷酸化p65的蛋白水平。总之,VDD通过激活核因子-κB信号通路加重慢性酒精性肝损伤。