为了评定补充精氨酸对精氨酸酶活性、肿瘤坏死因子-α（TNF-α）以及白介素-10（IL-10）合成的影响，巴西米纳斯吉拉斯联邦大学、奥斯瓦尔多·克鲁斯基金会勒内·拉舒研究中心通过对小鼠肠梗阻（IO）模型的脾巨噬细胞进行培养，同时利用一氧化氮合酶（iNOS）基因敲除动物对iNOS的抑制效应进行了研究。
该研究将雄性C57BL6/J野生型（WT）和iNOS基因敲除（iNOS-/-）小鼠随机分为6组：Sham组和Sham-/-组（标准喂养组）、IO组和IO-/-组（标准喂养＋IO）以及Arg组和Arg-/-组（补充精氨酸的标准喂养＋IO）。标准喂养或标准补充喂养处理后7天，IO模型建立。在培养的脾巨噬细胞中对精氨酸酶活性、TNF-α、IL-10水平进行了分析。
结果发现，补充精氨酸和缺乏iNOS可增加脾巨噬细胞的精氨酸酶活性（Arg、IO-/-和Arg-/-比Sham组，P＜0.05）。精氨酸还与降低TNF-α水平（Arg比IO组，P＜0.05）、维持IL-10水平（Arg比其他组，P＞0.05）有相关性。抑制iNOS对细胞因子浓度无影响（Sham-/-、IO-/-和Arg-/-比其他组，P＜0.05）。
因此，补充精氨酸和抑制iNOS可导致精氨酸酶活性增加，补充精氨酸可降低血清TNF-α水平，这可能与来源于精氨酸的一氧化氮有直接相关性。
JPEN J Parenter Enteral Nutr. 2016;40(3):417-22.
Arginine Supplementation Induces Arginase Activity and Inhibits TNF-α Synthesis in Mice Spleen Macrophages After Intestinal Obstruction.
Quirino IE, Carneiro MB, Cardoso VN, das Gracas Carvalho Dos Santos R, Vieira LQ, Fiuza JA, Alvarez-Leite JI, de Vasconcelos Generoso S, Correia MI.
Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; René Rachou Research Center, Fundacao Oswaldo Cruz, Belo Horizonte, MG, Brazil.
BACKGROUND: The purpose of this study was to assess the effect of arginine supplementation on arginase activity, tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) synthesis in cultured splenic macrophages from a murine model of intestinal obstruction (IO). The effects of nitric oxide synthase (iNOS) inhibition were also studied using iNOS knockout animals.
MATERIAL AND METHODS: Male C57BL6/J wild-type (WT) and iNOS knockout (iNOS-/-) mice were randomized into 6 groups: Sham and Sham-/- (standard chow), IO and IO-/- (standard chow + IO), and Arg and Arg-/- (standard chow supplemented with arginine + IO). After 7 days of treatment with standard or supplemented chow, IO was induced. Arginase activity as well as TNF-α and IL-10 levels were analyzed in splenic macrophage cultures.
RESULTS: Arginine supplementation and the absence of iNOS increased arginase activity in splenic macrophages (Arg, IO-/-, and Arg-/- groups vs the Sham group; P < .05). Arginine was also related to a decrease in TNF-α levels (Arg vs IO group, P < .05) and maintenance of IL-10 levels (Arg vs other groups, P > .05). The inhibition of iNOS did not result in effects on the concentration of cytokines (Sham-/-, IO-/-, and Arg-/- vs other, P < .05).
CONCLUSIONS: Arginine supplementation and iNOS inhibition led to increased arginase activity. Arginine availability decreased plasma TNF-α levels, which may be directly related to nitric oxide derived from arginine.
KEYWORDS: arginase; immune modulation; inducible nitric oxide synthase
PMID: 25135690
DOI: 10.1177/0148607114546374
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