肠梗阻后补充精氨酸可诱导小鼠脾巨噬细胞精氨酸酶活性并抑制肿瘤坏死因子合成

　　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