PREVENTIVE EFFECTS OF ASCORBIC ACID ON THE ISCHEMIA/REOXYGENATION INJURY IN THE RAT SMALL INTESTINE

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  • ラット小腸の虚血再酸素化傷害に対するアスコルビン酸の抑制効果について

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抄録

様々の臓器における虚血後再酸素化(ischemia/reoxygenation; I/R)時の細胞や機能の傷害は,発生する種々のフリーラジカルや,過酸化脂質によると考えられている.一方,アスコルビン酸(AsA)は,低濃度では過酸化を促進し,高濃度では逆に抑制することが知られている.ラット小腸においてI/R時の傷害の程度とAsAによる傷害抑制効果について生化学的,病理学的に検討した.AsAとグルタチオン(GSH)を,雄性Wistar系ラットに腹腔内投与し,60分後開腹,上腸間膜動脈を遮断し,全小腸を60分間虚血状態とした.再酸素化後20分で,全小腸を摘出して検索し,以下の結果をえた.AsA投与群では,過酸化脂質の産生は,有意に抑制され(LOOH Control: 26.30±1.98, AsA: 16.75±1.43 nmol/g tissue, p<0.01),また,glutaminase活性は,再酸素化後も有意に高く保たれ(Control: 0.41±0.04, AsA: 1.02±0.05μmol glutamate/h/mg tissue, p<0.05),組織傷害も軽微であった.また,還元型GSHレベルは,再酸素化後も高値に保たれた(Control:0.22±0.02, AsA:1.34±0.12μmol/g tissue, p<0.01).AsAは,ラット小腸において抗酸化剤として作用し,I/R傷害を軽減させることが明らかとなった.

Ischemia/reoxygenation (I/R) injury is observed in various organs, where some free radicals and lipid peroxides are believed to play an important role. We examined the preventive effects of ascorbic acid (AsA), one of antioxidant agents, on the I/R injury of the rat small intestine. AsA or glutathione was intraperitoneally administered to male Wistar rats weighing 250～300 g after one-day fasting. The entire small intestine was resected at three different points, just before ischemia, after ischemia, and after 20 min of reoxygenation. The specimens were used for the assays of lipid peroxides, glutathione, and glutaminase activity and for histological examination. In AsA-treated group, the production of lipid peroxides after reoxygenation was significantly suppressed and the ratio of reduced form of glutathione to the total glutathione was also significantly high. Tissue glutaminase activity decreased to less extent, and the degree of injury by reoxygenation was apparently less marked in this AsA-treated group. AsA works as an antioxidant against the peroxidative tissue injury possibly by scavenging free radicals and reducing the peroxidative reaction. The effects of AsA are expected to be very useful in small bowel transplantation and various surgical procedures.

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