Departamento de Fisiologia e Farmacologia, Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
Braz J Med Biol Res. 2009 Jun;42(6):567-73. doi: 10.1590/s0100-879x2009000600015.
We evaluated the effects of vincristine on the gastrointestinal (GI) motility of awake rats and correlated them with the course of vincristine-induced peripheral neuropathy. Vincristine or saline was injected into the tail vein of male Wistar rats (180-250 g) on alternate days: 50 microg/kg (5 doses, N = 10), 100 microg/kg (2, 3, 4 and 5 doses, N = 49) or 150 microg/kg (1, 2, or 5 doses, N = 37). Weight and stool output were measured daily for each animal. One day after completing the vincristine treatment, the animals were fasted for 24 h, gavage-fed with a test meal and sacrificed 10 min later to measure gastric emptying (GE), GI transit and colon weight. Sensory peripheral neuropathy was evaluated by hot plate testing. Chronic vincristine treatments with total cumulative doses of at least 250 microg/kg significantly decreased GE by 31-59% and GI transit by 55-93%. The effect of 5 doses of vincristine (150 microg/kg) on GE did not persist for more than 1 week. Colon weight increased after 2 and 5 doses of vincristine (150 microg/kg). Fecal output decreased up to 48 h after the fifth dose of vincristine (150 microg/kg). Vincristine decreased the heat pain threshold 1 day after 5 doses of 50-100 microg/kg or after 3-5 doses of 150 microg/kg. This effect lasted for at least 2 weeks after the fifth dose. Chronic intravenous vincristine treatment delayed GE and GI transit of liquid. This effect correlated with the peak increase in colon weight but not with the pain threshold changes.
我们评估了长春新碱对清醒大鼠胃肠道（GI）动力的影响，并将其与长春新碱诱导的周围神经病变的过程相关联。长春新碱或生理盐水通过尾静脉注射到雄性 Wistar 大鼠（180-250g）中，隔天一次：50μg/kg（5 个剂量，N=10），100μg/kg（2、3、4 和 5 个剂量，N=49）或 150μg/kg（1、2 或 5 个剂量，N=37）。每天为每只动物测量体重和粪便排出量。在完成长春新碱治疗后的一天，动物禁食 24 小时，经胃管给予测试餐，10 分钟后处死以测量胃排空（GE）、GI 转运和结肠重量。感觉周围神经病变通过热板测试进行评估。总累积剂量至少为 250μg/kg 的慢性长春新碱治疗显著降低了 31-59%的 GE 和 55-93%的 GI 转运。长春新碱（150μg/kg）5 个剂量对 GE 的影响在 1 周以上不会持续。长春新碱（150μg/kg）2 个和 5 个剂量后结肠重量增加。长春新碱（150μg/kg）第 5 个剂量后 48 小时内粪便排出量减少。50-100μg/kg 长春新碱 5 个剂量或 150μg/kg 长春新碱 3-5 个剂量后 1 天，长春新碱降低了热痛阈值。这种效应至少在第 5 个剂量后持续 2 周。慢性静脉内长春新碱治疗延迟了液体的 GE 和 GI 转运。这种效应与结肠重量的峰值增加相关，但与疼痛阈值的变化无关。
