伊立替康致小鼠消化与免疫系统不良反应研究
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摘要
目的:观察伊立替康(CPT-11)致小鼠消化与免疫系统不良反应的特点,为CPT-11所致不良反应的预防与治疗提供实验依据。方法:将24只雄性BALB/c小鼠按照体质量随机分为模型组和对照组,每组各12只。模型组给予腹腔注射CPT-11注射液[300 mg/(kg·d)]建立CPT-11不良反应的鼠模型,对照组给予腹腔注射等体积生理盐水。干预后第2天和第4天分别检测2组小鼠体质量、腹泻指数、脾指数和胸腺指数、外周血常规,采用HE染色法观察小鼠空肠、回肠、结肠的病理学改变。结果:干预后第2天和第4天,与对照组比较,模型组小鼠体质量明显减轻(P<0.05),腹泻指数明显增加(P<0.05),同时小鼠空肠、回肠和结肠黏膜出现不同程度的损伤,脾指数和胸腺指数明显降低(P<0.05),外周血中白细胞和中性粒细胞水平降低。结论:CPT-11可致小鼠消化与免疫系统不良反应,符合CPT-11的临床毒副反应,为CPT-11增效减毒的辅助用药的研发提供实验依据。
Objective:To investigate irinotecan(CPT-11)-induced side effects on the digestive and immune system of mice.Methods:24 male BABL/c mice were randomly divided into model group(n=12) and control group(n=12). The mice in the model group were given CPT-11 by intraperitoneal injection, the control group were given same volumes PBS by intraperitoneal injection.Body weight, diarrhea index, spleen index, thymus index, complete blood count and pathological changes of the jejunum, ileum and colon were measured on the second day and the fourth day after CPT-11 intervention. Results:Compared with the control group, mice body weight was decreased significantly on the second day and the fourth day upon CPT-11 intervention while diarrhea index was increased(P<0.05); CPT-11 intervention also decreased spleen index, thymus index(P<0.05), white blood cell count and neutrophil count profoundly along with significant jejunum, ileum and colon injury of the mice. Conclusion:CPT-11 can induce side effects about the digestive and immune system, which consistents with the clinical side effects of CPT-11, and this will be helpful for the further development of novel supplementary therapies for CPT-11 induced toxicity.
Objective:To investigate irinotecan(CPT-11)-induced side effects on the digestive and immune system of mice.Methods:24 male BABL/c mice were randomly divided into model group(n=12) and control group(n=12). The mice in the model group were given CPT-11 by intraperitoneal injection, the control group were given same volumes PBS by intraperitoneal injection.Body weight, diarrhea index, spleen index, thymus index, complete blood count and pathological changes of the jejunum, ileum and colon were measured on the second day and the fourth day after CPT-11 intervention. Results:Compared with the control group, mice body weight was decreased significantly on the second day and the fourth day upon CPT-11 intervention while diarrhea index was increased(P<0.05); CPT-11 intervention also decreased spleen index, thymus index(P<0.05), white blood cell count and neutrophil count profoundly along with significant jejunum, ileum and colon injury of the mice. Conclusion:CPT-11 can induce side effects about the digestive and immune system, which consistents with the clinical side effects of CPT-11, and this will be helpful for the further development of novel supplementary therapies for CPT-11 induced toxicity.
引文
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[19]卢惠明,高瑞珍,黄丽源.开普拓治疗晚期大肠癌的护理[J].护理学报,2002,9(2):51-52.
[20]张怡,李中东.伊立替康的不良反应及处理[J].中国药物警戒,2006,3(5):271-273.
[21]李利亚,贾立群,李学,等.伊立替康联合5-FU/CF治疗晚期结直肠癌的临床受益分析[J].中国癌症杂志,2006,16(1):49-51.
[22]王向涛,孙桂超,徐昶儒,等.龙葵多糖对荷瘤小鼠脾指数和胸腺指数的影响[J].哈尔滨商业大学学报(自然科学版),2014,30(5):513-516.
[23]梁秀宇.消风散对变应性接触性皮炎的抑制作用及其免疫学机制的实验研究[D].沈阳:辽宁中医药大学,2007:45-47.
[24]陈丽,焦顺昌.化疗对肿瘤免疫功能影响的研究进展[J].临床肿瘤学杂志,2011,16(9):853-856.
[2]于舒飞,王燕,胡兴胜,等.伊立替康联合奈达铂对比联合顺铂二线治疗复发或难治性小细胞肺癌的疗效及毒副作用回顾分析[J].中国肺癌杂志,2013,16(9):470-475.
[3]杨子长,王峰,何炜,等.含伊立替康方案一线治疗晚期胃癌的Meta分析[J].肿瘤,2015,2(2):205-213.
[4]陈丹丹,阳志军,李力.伊立替康在宫颈癌新辅助化疗中有效性和安全性的Meta分析[J].中国循证医学杂志,2015,15(10):1196-1201.
[5]刘娜,马天江,史磊,等.伊立替康单药治疗铂类耐药的复发卵巢癌疗效观察[J].中华实用诊断与治疗杂志,2013,27(2):176-177.
[6]ELTING L S,COOKSLEY C D,CHAMBERS M S,et al.Risk,outcomes,and costs of radiation-induced oral mucositis among patients with head-and-neck malignancies[J].Int J Radiat Oncol Biol Phys,2007,68(4):1110-1120.
[7]吴琼,叶华,朱宇珍,等.黄芩汤预防伊立替康所致迟发性腹泻的研究[J].中国实验方剂学杂志,2013,19(12):163-168.
[8]陶静,柳维林,黄佳,等.基于Notch1信号通路观察电针对脑缺血再灌注损伤大鼠缺血周边皮质与SVZ区神经干细胞增殖的影响[J].康复学报,2015,25(3):23-34.
[9]陈宏伟,包丽亚,黄月,等.清眩降压汤控制自发性高血压大鼠血压升高与抑制心肾大血管损害的药效学研究[J].康复学报,2017,27(2):28-32.
[10]LAM W,BUSSOM S,GUAN F,et al.The four-herb Chinese medicine PHY906 reduces chemotherapy-induced gastrointestinal toxicity[J].Sci Transl Med,2010,2(45):45-59.
[11]周干南,胡芝华,汪亚先,等.小鼠腹泻模型的制备与腹泻指数的应用[J].中草药,1994,25(4):195-196.
[12]SALTZ L B,COX J V,BLANKE C,et al.Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer[J].NEngl J Med,2000,343(13):905-914.
[13]开普拓临床研究协作组.开普拓治疗大肠癌的临床应用[J].中华肿瘤杂志,2003,25(6):607-609.
[14]王文明.伊立替康致小鼠迟发性腹泻模型的建立和中药干预的实验研究[D].合肥:安徽医科大学,2008:25-28.
[15]张晓光,张侠.盐酸伊立替康致迟发性腹泻作用机制及防治的研究进展[J].中国药物警戒,2012,9(9):535-538.
[16]KURITA A,KADO S,KANEDA N,et al.Modified irinotecan hydrochloride(CPT-11)administration schedule improves induction of delayed-onset diarrhea in rats[J].Cancer Chemother Pharmacol,2000,46(3):211-220.
[17]DRANITSARIS G,SHAH A,SPIROVSKI B,et al.Severe diarrhea in patients with advanced-stage colorectal cancer receiving FOLFOX or FOLFIRI chemotherapy:the development of a risk prediction tool[J].Clin Colorectal Cancer,2007,6(5):367-373.
[18]张程亮,高静,沈倩.预防和治疗伊立替康所致腹泻的研究进展[J].中国药学杂志,2010,45(22):1704-1707.
[19]卢惠明,高瑞珍,黄丽源.开普拓治疗晚期大肠癌的护理[J].护理学报,2002,9(2):51-52.
[20]张怡,李中东.伊立替康的不良反应及处理[J].中国药物警戒,2006,3(5):271-273.
[21]李利亚,贾立群,李学,等.伊立替康联合5-FU/CF治疗晚期结直肠癌的临床受益分析[J].中国癌症杂志,2006,16(1):49-51.
[22]王向涛,孙桂超,徐昶儒,等.龙葵多糖对荷瘤小鼠脾指数和胸腺指数的影响[J].哈尔滨商业大学学报(自然科学版),2014,30(5):513-516.
[23]梁秀宇.消风散对变应性接触性皮炎的抑制作用及其免疫学机制的实验研究[D].沈阳:辽宁中医药大学,2007:45-47.
[24]陈丽,焦顺昌.化疗对肿瘤免疫功能影响的研究进展[J].临床肿瘤学杂志,2011,16(9):853-856.