The mechanism of the susceptibility to infection in diabetes and the new management

糖尿病感染易感机制及新管理

• 批准号: 09671023
• 负责人: SATO Noriyuki
• 金额: $ 0.32万
• 依托单位: DOKKYO UNIVERSITY SCHOOL OF MEDICINE (1998)Gunma University (1997)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671023/
• 关键词: Diabetes Mellitus; Neutrophils; Oxygen-derived free radicals; infection; New management; 易感染性; 活性酸素; ミエロペルオキシダーゼ; レプチン

In poorly controlled diabetic patients and streptozotocin-induced diabetic rats, neutrophil bactericidal function (oxygen-derived free radicals generation) was clearly decreased. Especially, the generation of superoxide anion and the myeloperoxidase (MPO) dependent radicals were reduced compaired to control. The MPO activity was also decreased in neutrophils from poorly controlled diabetic patients, which was correlated to the increase in HbA1c.Two drugs, granulocyte-colony stimulating facto (G-CSF) and epairestat, an aldose reductase inhibitor, were improved the diabetic-induced decrease in the generation of oxygen-derived free radicals by poorly controlled diabetic patients and diabetic rats. This improvement by G-CSF was more significant in patients with more poorly blood glucose control. In diabetic rats, cytosolic sorbitol concentration was increased. Epalrestat not only suppressed this increase in sorbitol concentration but increased the impaired neutrophil bactericidal function. There was a negative correlation between epairestat-induced decrease in sorbitol concentration and epairestat-induced increase in neutrophil bactericidal function.It is well known that the susceptibility to infection is dependent on the impaired neutrophils bactericidal function. This study suggested that the susceptibility to infection in diabetes may be due to the impairment of the generation of oxygen-derived free radicals by neutrophils. Some drugs (e.g. (G-CSF and epairestat) may be useful as drug to prevent the susceptibility to infection in diabetes.

在控制不良的糖尿病患者和链脲佐菌素诱导的糖尿病大鼠中，中性粒细胞的杀菌功能（氧源自由基的产生）明显下降。特别是，与对照组相比，超氧阴离子和髓过氧化物酶（MPO）依赖自由基的产生减少。控制不良的糖尿病患者的中性粒细胞MPO活性也降低，这与HbA1c升高有关。两种药物，粒细胞集落刺激因子（G-CSF）和醛糖还原酶抑制剂依帕司他（epairestat），可以改善糖尿病患者和糖尿病大鼠在糖尿病诱导的氧源性自由基生成的减少。G-CSF的这种改善在血糖控制较差的患者中更为显著。糖尿病大鼠细胞内山梨醇浓度升高。依帕司他不仅抑制山梨醇浓度的增加，而且增加了受损的中性粒细胞杀菌功能。epairestat诱导的山梨醇浓度下降与epairestat诱导的中性粒细胞杀菌功能增加呈负相关。众所周知，对感染的易感性依赖于中性粒细胞杀菌功能的受损。本研究提示糖尿病患者对感染的易感性可能是由于中性粒细胞产生氧源自由基的功能受损。一些药物（如G-CSF和伊替司他）可作为预防糖尿病易感性感染的药物。

项目成果

佐藤則之、 森 昌朋: "ミエロペルオキシダーゼ" 日本臨床. 56. 246-250 (1998)

Noriyuki Sato、Masatomo Mori：“髓过氧化物酶”日本临床杂志 56. 246-250 (1998)。

Sato,N., Kashima,K., Tanaka,Y., Shimizu,H., Mori,M.: "Effect of Granulocyte-colony stimulating factor on generation of oxygen-derived free radicals and myeloperoxidase activity in neutrophils from poorly controlled NIDDM patients" Diabetes. 46. 133-137 (1

Sato,N.、Kashima,K.、Tanaka,Y.、Shimizu,H.、Mori,M.：“粒细胞集落刺激因子对 NIDDM 控制不良的中性粒细胞中氧自由基生成和髓过氧化物酶活性的影响

佐藤 則之.清水 弘行.森 昌朋: "ミエロペルオキシダーゼ" 日本臨床(増刊号)糖尿病3. 728号. 246-250 (1998)

Noriyuki Sato。Hiroyuki Shimizu。Masayuki Mori：“髓过氧化物酶”日本临床（特刊）糖尿病 3. No. 728. 246-250 (1998)

佐藤 則之, 森 昌朋: "甲状腺刺激ホルモン(TSH)" 臨床スポーツ医学(臨時増刊号)スポーツと臨床検査. 14巻. 115-117 (1997)

Noriyuki Sato，Masatomo Mori：“促甲状腺激素（TSH）”临床运动医学（特刊）运动和临床测试第 14 卷。115-117（1997 年）

上原豊、 佐藤則之、 森昌朋: "顆粒球エラスターゼ" 日本臨床. 56. 241-245 (1998)

Yutaka Uehara、Noriyuki Sato 和 Masatomo Mori：“粒细胞弹性蛋白酶”日本临床杂志 56. 241-245 (1998)。