Milk osteopontin, a nutritional approach to prevent alcohol-induced liver injury
Milk osteopontin, a nutritional approach to prevent alcohol-induced liver injury
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DOI：
10.1152/ajpgi.00014.2013
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发表时间：
2013-05-01
影响因子：
4.5
通讯作者：
Nieto, Natalia
中科院分区：
文献类型：
--
作者：
Ge, Xiaodong;Lu, Yongke;Nieto, Natalia
饮酒是全世界肝病的主要原因；因此，迫切需要开发新的治疗干预措施。酒精性肝病发病和进展的关键事件部分是由肠道与肝脏的相互作用引起的。骨桥蛋白是一种高浓度存在于人乳、脐带和婴儿血浆中的细胞因子，具有有益的潜力。我们假设，通过饮食摄入牛奶骨桥蛋白可以通过维持肠道完整性并避免肝脏炎症和脂肪变性来预防酒精引起的肝损伤。野生型小鼠单独喂食对照或乙醇 Lieber-DeCarli 饮食或与牛奶骨桥蛋白组合喂养 3 周，并测量肠道和肝脏损伤的参数。牛奶骨桥蛋白除了降低酒精喂养小鼠粘膜和粘膜下层中的巨噬细胞、浆细胞、淋巴细胞和中性粒细胞外，还通过增加腺体高度、隐窝细胞和肠上皮细胞增殖和粘蛋白含量来保护胃和肠道。牛奶骨桥蛋白靶向肠肝轴，保留酒精喂养小鼠中紧密连接蛋白的表达，从而维持肠道完整性和通透性。与乙醇喂养的小鼠相比，联合治疗组的转氨酶、活性评分、甘油三酯水平、中性粒细胞浸润、3-硝基酪氨酸残基、脂质过氧化终产物、革兰氏阴性菌易位、脂多糖水平和肿瘤坏死因子-α均较低，因此可防止肝损伤。此外，牛奶骨桥蛋白可减轻 OPN 敲除小鼠中乙醇介导的肝损伤。牛奶骨桥蛋白可能是一种简单有效的营养治疗策略，可预防酒精肝毒性，其中包括肠道保护、抗炎和抗脂肪变性作用。
Alcohol consumption is a leading cause of liver disease worldwide; thus, there is an urgent need to develop novel therapeutic interventions. Key events for the onset and progression of alcoholic liver disease result in part from the gut-to-liver interaction. Osteopontin is a cytokine present at high concentration in human milk, umbilical cord, and infants' plasma with beneficial potential. We hypothesized that dietary administration of milk osteopontin could prevent alcohol-induced liver injury perhaps by maintaining gut integrity and averting hepatic inflammation and steatosis. Wild-type mice were fed either the control or the ethanol Lieber-DeCarli diets alone or in combination with milk osteopontin for 3 wk, and parameters of gut and liver damage were measured. Milk osteopontin protected the stomach and the gut by increasing gland height, crypt cell plus enterocyte proliferation, and mucin content in addition to lowering macrophages, plasmacytes, lymphocytes, and neutrophils in the mucosa and submucosa in alcohol-fed mice. Milk osteopontin targeted the gut-liver axis, preserving the expression of tight-junction proteins in alcohol-fed mice thus maintaining intestinal integrity and permeability. There was protection from liver injury since transaminases, the activity scores, triglyceride levels, neutrophil infiltration, 3-nitrotyrosine residues, lipid peroxidation end products, translocation of gram-negative bacteria, lipopolysaccharide levels, and tumor necrosis factor-alpha were lower in cotreated than in ethanol-fed mice. Furthermore, milk osteopontin diminished ethanol-mediated liver injury in OPN knockout mice. Milk osteopontin could be a simple effective nutritional therapeutic strategy to prevent alcohol hepatotoxicity due, among others, to gut protective, anti-inflammatory, and anti-steatotic actions.