Área de Histología Humana y Anatomía Patológica, Departamento de Ciencias Básicas de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain.
Unidad del Dolor, Servicio de Anestesia, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Neurogastroenterol Motil. 2018 Nov;30(11):e13399. doi: 10.1111/nmo.13399. Epub 2018 Jul 4.
Vincristine is a commonly used chemotherapeutic agent. It is associated with undesirable digestive side effects. However, the impact of vincristine on gastrointestinal structure and motility or its long-term effects have not been deeply studied in animal models. This could be useful in order to develop therapeutic or preventive strategies for cancer patients. The aim of this study was to analyze such effects.
Rats received saline or vincristine (0.1 mg kg , ip) daily for 10 days. Evaluations were performed during treatment and 2-6 weeks after. Somatic mechano-sensitivity was assessed using von Frey hairs. Gastrointestinal motor function was studied by means of radiographic still images and colonic propulsion of fecal pellets using fluoroscopy videos. Histological assessment of the gut morphology and immunohistochemistry for HuC/D and nNOS were performed in whole-mount myenteric plexus preparations.
Peripheral sensitivity was increased in animals treated with vincristine and did not subside 2 weeks after treatment finalization. Vincristine treatment inhibited gastrointestinal motility although this was recovered to normal values with time. Damage in the digestive wall after vincristine treatment was greater in the ileum than in the colon. Villi shortening (in ileum) and large inflammatory nodules still remained 2 weeks after treatment finalization. Finally, the proportion of nNOS-immunoreactive neurons was increased with vincristine and continued to be increased 2 weeks after treatment finalization.
Vincristine alters gastrointestinal motility, peripheral sensitivity and mucosal architecture. Vincristine-induced neuropathy (somatic and enteric), intestinal mucosa damage and inflammatory infiltrations are relatively long-lasting.
长春新碱是一种常用的化疗药物。它与不良的消化道副作用有关。然而，长春新碱对胃肠结构和运动的影响或其长期影响在动物模型中尚未得到深入研究。这对于为癌症患者开发治疗或预防策略可能很有用。本研究的目的是分析这些影响。
大鼠每天接受生理盐水或长春新碱（0.1mg/kg，ip）治疗 10 天。在治疗期间和治疗结束后 2-6 周进行评估。使用 von Frey 毛发评估躯体机械感觉敏感性。通过射线照相静态图像和荧光透视视频研究胃肠道运动功能，以评估粪便颗粒的结肠推进。在整个肌间神经丛制剂中进行肠道形态学的组织学评估和 HuC/D 和 nNOS 的免疫组织化学。
用长春新碱治疗的动物外周敏感性增加，并且在治疗结束后 2 周仍未消退。长春新碱治疗抑制了胃肠道运动，尽管随着时间的推移恢复到正常值。与结肠相比，长春新碱治疗后消化壁的损伤在回肠中更大。绒毛缩短（在回肠中）和大的炎症性结节在治疗结束后 2 周仍然存在。最后，用长春新碱治疗后 nNOS 免疫反应性神经元的比例增加，并在治疗结束后 2 周继续增加。
长春新碱改变了胃肠道运动、外周敏感性和黏膜结构。长春新碱诱导的神经病变（躯体和肠）、肠黏膜损伤和炎症浸润相对持久。
