Gomes T N, Santos C C, Souza-Filho M V, Cunha F Q, Ribeiro R A
Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
Braz J Med Biol Res. 1995 Oct;28(10):1103-8.
The involvement of cytokines TNF-alpha and IL-1 has been investigated in a mouse model of cyclophosphamide (CYP)-induced hemorrhagic cystitis. Male Swiss mice (25-30 g) received CYP in a single i.p. dose of 100, 200 or 400 mg/kg and were sacrificed 6, 12, 24, 48 and 72 h later. Cystitis was evaluated by determining the changes in bladder wet weight (BW) and plasma protein extravasation (PPE, measured by the Evans blue leakage technique). CYP treatment induced a marked increase in BW and in PPE, which was significant within 6 h and reached maximal values within 12 h (BW, 118%, P < 0.05; N = 11; and PPE, 824%, P < 0.05; N = 11), continuing to be significant until 48 h. Pretreatment of animals with whole anti-TNF-alpha serum (25 or 50 microliters diluted in 500 microliters 0.9% saline, i.p., 30 min earlier) caused a significant reduction in the CYP-induced BW increase in 6-h and 12-h cystitis (82% and 91%, respectively, P < 0.05; N = 6) and in the CYP-induced PPE increase (60% and 52%, respectively, P < 0.05; N = 6). In addition, the administration of whole anti-IL- 1 beta serum at the same dose promoted a significant blockage of the CYP-induced increase in BW (47%, P < 0.05; N = 6) and PPE increase (41%, P < 0.05; N = 6) only in 12-h cystitis. The control serum did not modify the effect of CYP. Histopathologic analysis of the bladders from anti-TNF-alpha- and anti-IL-1 beta-pretreated groups revealed a significant reduction of the following parameters compared to the control groups: mucosal erosion, hemorrhage, edema, leukocyte migration, fibrin deposition and ulcerations. These results suggests that TNF-alpha and IL-1 are crucial mediators involved in inflammatory events occurring in CYP-induced hemorrhagic cystitis.
在环磷酰胺（CYP）诱导的出血性膀胱炎小鼠模型中，对细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-1（IL-1）的作用进行了研究。雄性瑞士小鼠（25 - 30克）腹腔注射单次剂量为100、200或400毫克/千克的CYP，在6、12、24、48和72小时后处死。通过测定膀胱湿重（BW）的变化和血浆蛋白外渗（PPE，采用伊文思蓝渗漏技术测量）来评估膀胱炎。CYP处理导致BW和PPE显著增加，6小时内显著升高，12小时内达到最大值（BW为118%，P < 0.05；N = 11；PPE为824%，P < 0.05；N = 11），直至48小时仍保持显著。用全抗TNF-α血清预处理动物（25或50微升在500微升0.9%盐水中稀释，腹腔注射，提前30分钟），导致CYP诱导的6小时和12小时膀胱炎中BW增加显著降低（分别为82%和91%，P < 0.05；N = 6），以及CYP诱导的PPE增加显著降低（分别为60%和52%，P < 0.05；N = 6）。此外，以相同剂量给予全抗IL-1β血清仅在12小时膀胱炎中显著阻断了CYP诱导的BW增加（47%，P < 0.05；N = 6）和PPE增加（41%，P < 0.05；N = 6）。对照血清未改变CYP的作用。与对照组相比，抗TNF-α和抗IL-1β预处理组膀胱的组织病理学分析显示以下参数显著降低：黏膜糜烂、出血、水肿、白细胞迁移、纤维蛋白沉积和溃疡。这些结果表明，TNF-α和IL-1是参与CYP诱导的出血性膀胱炎中炎症事件的关键介质。
