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摘要：
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摘要：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（non-
alcoholic 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（non-
alcoholic steatohepatitis，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。
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Abstract: 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.
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