维生素D缺乏与非酒精性脂肪性肝病的关系及机制

Relationship between vitamin D deficiency and non-alcoholic fatty liver disease and its mechanism

随着社会经济的快速发展及生活习惯的改变,肥胖、2型糖尿病和非酒精性脂肪性肝病(nonalcoholic fatty liver diseases,NAFLD)在国内流行。流行病学调查表明,中国成人不同程度肥胖、2型糖尿病及脂肪肝者占15%或更高。NAFLD是一类脂肪性肝脏疾病的总称,与饮酒无关,其共性是甘油三酯在肝实质细胞的大量堆积。10%～20%NAFLD患者可能进展为非酒精性脂肪性肝炎(nonalcoholicsteatohepatitis,NASH),后者中约20%可能进一步进展为肝硬化甚至肝细胞癌。Day等于1998年提出了"二次打击学说"来解释脂肪性肝炎的形成。大量调查显示,维生素D缺乏与脂肪肝和代谢综合征的发生密切相关,但作用机制尚未明确。维生素D受体(vitamin D receptor,VDR)在回肠帕内特细胞(Paneth cells)中大量表达,提示维生素D信号在小肠的先天性免疫及平衡肠道菌群方面发挥关键作用。近年来,动物模型研究发现充足的维生素D可促进帕内特细胞外分泌抗菌肽(alpha-defensins),平衡肠道菌群,减少内毒素入血,从而预防脂肪肝的形成。此外,有研究表明维生素D信号能够诱导调节性T细胞(regulatory T cells,Tregs),抑制Th1及Th17应答,维持机体免疫平衡。因此,开展大规模临床试验来验证维生素D对NAFLD的疗效及分子机制十分必要。

With the rapid development of social economy and the change of lifestyles,obesity,type 2 diabetes and non-alcoholic fatty liver disease(NAFLD)become popular in China.Epidemiological investigation in China showed that about 15% or higher adults have different degrees of obesity,type 2 diabetes and fatty liver disease.NAFLD is the sum of a class of fatty liver diseases,unrelated to alcohol consumption.The commonality of NAFLD is a large number accumulation of triglycerides in liver parenchyma cells.About 10%~20% patients with NAFLD could develop into non-alcoholic fatty hepatitis(NASH),20% of which possibly progress to liver cirrhosis or even hepatocellular carcinoma.Day et al.put forward the “two-hit hypothesis” in 1998 to explain the formation of fatty hepatitis.Many surveys showed that vitamin D deficiency had close relationship with the incidence of fatty liver disease and metabolic syndrome,but the mechanism was not clear.Vitamin D receptor(VDR)abundantly expressed in the ileum Paneth cells,which indicated that vitamin D played a key role in the innate immune of small intestine and the balance of gut microbiota.In recent years,we found that sufficient vitamin D could enhance Paneth cells secreting antibacterial peptide(alpha-defensins)in animal model,which could balance the intestinal flora and reduce endotoxin in the blood to resist fatty liver.In addition,the reports showed that vitamin D signal could induce regulatory T cells(Tregs),and inhibit Th1 and Th17 response in order to maintain the body’s immune balance.Therefore,it is necessary to carry out large-scale clinical trials to test the effects of vitamin D for the treatment of fatty liver disease and the role of molecular mechanism.