Sido B, Hack V, Hochlehnert A, Lipps H, Herfarth C, Dröge W
Department of Surgery, University of Heidelberg, Germany.
Gut. 1998 Apr;42(4):485-92. doi: 10.1136/gut.42.4.485.
Reactive oxygen species contribute to tissue injury in inflammatory bowel disease (IBD). The tripeptide glutathione (GSH) is the most important intracellular antioxidant.
To investigate constituent amino acid plasma levels and the GSH redox status in different compartments in IBD with emphasis on intestinal GSH synthesis in Crohn's disease.
Precursor amino acid levels were analysed in plasma and intestinal mucosa. Reduced (rGSH) and oxidised glutathione (GSSG) were determined enzymatically in peripheral blood mononuclear cells (PBMC), red blood cells (RBC), muscle, and in non-inflamed and inflamed ileum mucosa. Mucosal enzyme activity of gamma-glutamylcysteine synthetase (gamma GCS) and gamma-glutamyl transferase (gamma GT) was analysed. Blood of healthy subjects and normal mucosa from a bowel segment resected for tumor growth were used as controls.
Abnormally low plasma cysteine and cystine levels were associated with inflammation in IBD (p < 10(-4)). Decreased rGSH levels were demonstrated in non-inflamed mucosa (p < 0.01) and inflamed mucosa (p = 10(-6)) in patients with IBD, while GSSG increased with inflammation (p = 0.007) compared with controls. Enzyme activity of gamma GCS was reduced in non-inflamed mucosa (p < 0.01) and, along with gamma GT, in inflamed mucosa (p < 10(-4)). The GSH content was unchanged in PBMC, RBC, and muscle.
Decreased activity of key enzymes involved in GSH synthesis accompanied by a decreased availability of cyst(e)ine for GSH synthesis contribute to mucosal GSH deficiency in IBD. As the impaired mucosal antioxidative capacity may further promote oxidative damage, GSH deficiency might be a target for therapeutic intervention in IBD.
活性氧会导致炎症性肠病（IBD）的组织损伤。三肽谷胱甘肽（GSH）是最重要的细胞内抗氧化剂。
研究IBD不同部位的组成氨基酸血浆水平和GSH氧化还原状态，重点关注克罗恩病肠道GSH的合成。
分析血浆和肠黏膜中前体氨基酸水平。采用酶法测定外周血单核细胞（PBMC）、红细胞（RBC）、肌肉以及非炎症和炎症回肠黏膜中的还原型谷胱甘肽（rGSH）和氧化型谷胱甘肽（GSSG）。分析γ-谷氨酰半胱氨酸合成酶（γGCS）和γ-谷氨酰转移酶（γGT）的黏膜酶活性。以健康受试者的血液和因肿瘤生长而切除的肠段正常黏膜作为对照。
IBD患者血浆中半胱氨酸和胱氨酸水平异常降低与炎症相关（p < 10⁻⁴）。IBD患者非炎症黏膜（p < 0.01）和炎症黏膜（p = 10⁻⁶）中rGSH水平降低，而与对照组相比，GSSG随炎症增加（p = 0.007）。γGCS的酶活性在非炎症黏膜中降低（p < 0.01），在炎症黏膜中与γGT一起降低（p < 10⁻⁴）。PBMC、RBC和肌肉中的GSH含量未改变。
参与GSH合成的关键酶活性降低，同时用于GSH合成的半胱氨酸可用性降低，导致IBD患者黏膜GSH缺乏。由于受损的黏膜抗氧化能力可能进一步促进氧化损伤，GSH缺乏可能是IBD治疗干预的靶点。
