卡培他滨诱导手足综合征动物模型的建立  

Establishment of an animal model of hand foot syndrome induced by capecitabine

作　　者：黎鹏[1] 王炳胜[1] 李永民[1] 

机构地区：[1]河北北方学院研究生院,河北张家口075000

出　　处：《中华肿瘤防治杂志》2017年第12期802-807,共6页Chinese Journal of Cancer Prevention and Treatment

基　　金：全军"十二五"中医药重点项目(10ZYZ105);河北省研究生创新资助项目(285)

摘　　要：目的卡培他滨作为一线化疗药物,诱发手足综合征(hand foot syndrome,HFS)的发病率高,但目前HFS的发病机制不清,临床研究过程中相关标本(尤其是病理标本)难以获得。本研究旨在建立理想卡培他滨诱导HFS大鼠模型,从而应用于卡培他滨致HFS的发病机制及防治措施的研究中。方法 SD雌性大鼠115只,按实验需求分为A、B、C、D、E、F 6组,A组以200mg/kg卡培他滨灌胃连续7d,2次/d,休息3d。B组在A组基础上再灌胃7d,建立卡培他滨诱导HFS大鼠模型,C组400mg/kg,灌胃连续7d,2次/d。D、E组为空白对照组,F组为正常对照组。通过图像对比,HE染色和天狼猩红染色等方法对比评价所建立HFS模型。结果 A组HFS发生率为40.0%,B组总发病率可达到77.5%,C组HFS发病率可达到80.0%,D、E、F组HFS发病率均为0。经统计学分析,A组与B、C两组相比HFS发病率差异有统计学意义,P<0.001;B组与C组相比HFS发病率差异无统计学意义,P=1.000。但是,C组大鼠第1个周期平均体质量(F=6.779 3,P<0.001)与第2个周期平均体质量(F=23.611 1,P<0.001)均明显低于B组。结论与200mg/kg卡培他滨灌胃,给药2个周期相比,200 mg/kg卡培他滨灌胃给药1个周期,HFS的发病率较低,而400mg/kg卡培他滨灌胃给药2个周期,并不能增加造模成功率,而且增加了造模成本,引起不良反应发生增加。因此,200mg/kg卡培他滨灌胃给药2个周期的造模方法,在不增加造模成本的同时,既保证了高的造模成功率(77.5%),也不会致模型大鼠出现严重的给药不良反应,能够建立质量较高的卡培他滨诱导HFS的大鼠模型。OBJECTIVE Capecitabine is the first-line chemotherapy drug,that induced a high incidence of hand-foot syndrome（HFS）,but the pathogenesis of HFS is unclear now,clinical research related specimens（especially the pathological specimens）is difficult to obtain.The aim of this study was to establish a rat model of hand foot syndrome induced by the capecitabine which was used in the study of the pathogenesis,prevention and treatment of the HFS.METHODS Totally 115 female SD rats were divided into group A,B,C,D,E and F.Group A and B was respectively given 200mg/kg capecitabine in one cycle and two cycles with the method of gavage.Group C was controlled with large dose（400mg/kg）,group D and E was vacuity contrast group,group F was the normal control group.Further more,to evaluated the model by comparing the image,He staining,sirius red staining.RESULTS The incidence of HFS in group A was 40.0%,in group B was 77.5%,in group C was 80.0%,and the incidence of HFS in D,E,F was 0.With statistical analysis,there was a significant difference in the incidence of HFS between group A and group B,C（P〈0.001）,but there was no significant difference in the incidence of HFS between group B and group C（P=1.000）.However,the average weight of group C in the first cycle（F=6.779 3,P〈0.001）and the second cycle（F=23.611 1,P〈0.001）were both significantly lower than the group B.CONCLUSIONS Compared to the rats that was given 200mg/kg capecitabine with for 2cycles,the incidence of HFS is lower in the rats that was given 200 mg/kg capecitabine for 1cycle,but the method that with400mg/kg capecitabine for 2cycles can not improve the rate of model and increase the side effects and the cost of modeling.So,the high quality hand foot syndrome model can be established with 200 mg/kg capecitabine for two cycles in a high success rate with not increasing the modeling costs and side effects.

关 键 词：卡培他滨 手足综合征 造模方法 动物模型 

分 类 号：R-332[医药卫生] R730.53