Urinary Tract Infection, Reserch of Infection Mechanism and Its Applicatin

尿路感染、感染机制研究及其应用

• 批准号: 06671597
• 负责人: MATSUMOTO Tetsuro
• 金额: $ 1.09万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671597/
• 关键词: pyelonephritis; Bacterial pili; Renal scarring; Polymorphonuclear leukocyte; Adhesin; Active oxygen; Biofilm; New quinolone; 腎孟腎炎; 活性酵素; 白血球; 高浸透圧; NADPH Oxidase; Superoxide

Gene cloning of bacterial pili of Eschrichia coli or Serratia marcescens was performed, and effect of structure of adhesine and bacterial pili on the experimental pyelonephritis was investigated. The adhesine on the MS-piliated bacteria of Eschrichia coli and Serratia marcescens stringly stimulated scar formation following pyelonephritis, suggesting that the MS-adhesin stimulated polymorhonuclearleukocytes (PMNs) in the infected site, and PMNs released active oxygen speceis resulting tissue injury arround renal tissue. Renal scarring following infection with MS-piliated bacteria was suppressed by scavengers of superoxide such as CV3611, Ebselen, Steroid and ulinastatin. These scavengers were effective at the combination of antimicrobial agents.PMN-function was suppressed in the renal medulla due to hyperosmolality. The mechanism of suppression of PMNs were thought to be ATP exhausion at Na or direct inactivation at urea. Ofloxacin and fleroxacin, new quinolone antimicrobials, enhanced PMN-function even in hyperosmotic condition, suggesting that these agents were more effective in the treatment of pyelonephritis.

对大肠杆菌和粘质沙雷氏菌的细菌皮利进行了基因克隆，并研究了粘附素和细菌皮利结构对实验性肾盂肾炎的影响。大肠杆菌和粘质沙雷氏菌的MS菌毛上的粘附素强烈刺激肾盂肾炎后的瘢痕形成，提示MS粘附素刺激感染部位的多形核白细胞（PMNs），PMNs释放活性氧，导致肾组织周围的组织损伤。超氧化物清除剂如CV3611、Ebselen、类固醇和乌司他丁可抑制MS纤毛菌感染后的肾瘢痕形成。这些清除剂在抗菌药物的组合中是有效的。由于高渗透压，肾髓质中的PMN功能被抑制。其抑制机制可能是ATP对Na+的抑制或对尿素的直接失活。氧氟沙星和氟罗沙星，新的喹诺酮类抗菌药物，即使在高渗条件下，增强中性粒细胞功能，这表明这些药物是更有效的治疗肾盂肾炎。

项目成果

Matsumot, Tel al: "Ofloxacin and fleroxacin enhance superoxide production human polymorphonuckar leukocytes by increasing phosphorylaion in the signal transduction patyway" International Journal of Antimicrobial Agents. 6. 85-89 (1995)

Matsumot，Tel al：“氧氟沙星和氟罗沙星通过增加信号转导途径中的磷酸化来增强人多形努克白细胞的超氧化物产生”《国际抗菌药物杂志》。

松本哲朗: "今日の治療指針" 医学書院(分指執筆), 2 (1994)

松本哲朗：“当今的治疗指南”Igakushoin（文藏着），2（1994）

Matsumoto T et al.: "Restorative effect of ofloxacin on the inhibited chemiluminescence response of neutrophils by sera from uremic patients" Drugs. 49. 75-77 (1995)

Matsumoto T 等人：“氧氟沙星对尿毒症患者血清抑制的中性粒细胞化学发光反应的恢复作用”药物。

Matsumot, T eT al.: "Res torative effect of ofloxacin on the inhibited chemiluminescence response of neutrophils by sera from uremic patinets." Drugs. 49. 75-77 (1995)

Matsumot, T et al.：“氧氟沙星对尿毒症病人血清抑制的中性粒细胞化学发光反应的恢复作用。”

Matsumot, T et al.: "Preventive effect of ulinastain on renal scarring in rat. model of yelonephritis induced by direct crascending infection with Serratiamarcescens or..." Nephron. 69. 65-70 (1995)

Matsumot, T 等人：“乌那司他对大鼠肾疤痕的预防作用。粘质沙雷氏菌直接爬行感染诱导的肾盂肾炎模型或……”肾单位。