支链氨基酸和微量元素对非酒精性脂肪性肝炎小鼠有抗氧化作用

　　为了阐明单独或同时给予富含抗氧化剂的营养素，包括支链氨基酸（BCAA）、微量元素、维生素，对非酒精性脂肪性肝炎（NASH）小鼠模型的肝功能是否有积极影响，并确定产生这些作用的机制，日本久留米大学、朝倉医師会病院开展了一项研究。

　　该研究给予7周龄雄性KKAy小鼠缺乏蛋氨酸和胆碱的饮食（MCD）4周后将其分为7组继续喂养4周：A组（正常饮食）、B组（MCD；对照）、C组（MCD＋微量元素）、D组（MCD＋BCAA）、E组（MCD＋微量元素＋BCAA）、F组（MCD＋微量元素＋BCAA＋维生素）。随后，对每组小鼠肝脏标本中的8-羟-2'-脱氧鸟苷（8-OHdG）和4-羟-2'-壬烯醛（4-HNE）进行生物化学分析、组织学分析、免疫组织化学分析，对胰岛素葡萄糖信号转导、脂质代谢、内质网（ER）应激相关信号转导进行了蛋白质印迹分析。

　　结果发现，D～F组的所有NASH相关分析结果形态学分级、8-OHdG免疫定位平均程度显著低于B组。E和F组的胰岛素受体β亚基（IRβ）和磷酸化延伸因子（p-elF）、F组的磷脂酰肌醇3激酶（PI3K85）和磷酸化乙酰辅酶A（p-AcelCoA）和磷酸化蛋白激酶核糖核酸样内质网激酶（PERK）表达水平与A组相似。

　　因此，联合给予富含抗氧化剂的营养素，包括BCAA和微量元素，通过减少氧化应激（主要通过下调内质网应激通路）可能抑制NASH进展。

JPEN J Parenter Enteral Nutr. 2016;40(4):519-28.

Branched-Chain Amino Acid-Rich Supplements Containing Microelements Have Antioxidant Effects on Nonalcoholic Steatohepatitis in Mice.

Tanaka H, Fukahori S, Baba S, Ueno T, Sivakumar R, Yagi M, Asagiri K, Ishii S, Tanaka Y.

Kurume University School of Medicine, Kurume, Japan; Asakura Medical Association Hospital, Fukuoka, Japan.

BACKGROUND: The aim of the present study was to elucidate whether the administration of antioxidant-rich nutrients, including branched-chain amino acids (BCAAs), microelements, and vitamins, both alone and in combination, has a positive impact on liver function in a nonalcoholic steatohepatitis (NASH) mouse model and identify the mechanisms underlying these effects.

METHODS: Seven-week-old male KKAy mice fed a methionine- and choline-deficient diet (MCD) for 4 weeks were divided into 7 groups and fed the following planned diets for another 4 weeks: group A (normal diet), group B (MCD; control), group C (MCD with rich microelements), group D (MCD with rich BCAAs), group E (MCD with rich microelements and BCAAs), and group F (MCD with rich microelements, BCAAs, and vitamins). We then conducted biochemical assays, histological analyses, immunohistochemistry for 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4-hydroxy-2'-nonenal (4-HNE), and Western blotting for insulin glucose signaling, lipid metabolism, and endoplasmic reticulum (ER) stress-related signaling in liver specimens obtained from mice in each group.

RESULTS: The morphometric grades of all NASH-related findings and the mean degree of 8-OHdG immunolocalization in groups D-F were significantly lower than those observed in group B. The expression levels of insulin receptor β subunit (IRβ) and p-elF in groups E and F and those of phosphatidyl-inositol 3 kinase (PI3K85), p-AcelCoA, and PERK in group F were similar to those noted in group A.

CONCLUSIONS: The administration of a combination of antioxidant-rich nutrients, including BCAAs and microelements, is likely to suppress the progression of NASH by reducing oxidative stress, primarily via the downregulation of the ER stress pathway.

PMID: 25316683

DOI: 10.1177/0148607114555160