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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 a first-line chemotherapeutic drug that causes a high incidence of hand foot syndrome (HFS). However, the current pathogenesis of HFS is unclear. It is difficult to obtain relevant specimens (especially pathological specimens) during clinical research. This study aimed to establish ideal capecitabine-induced HFS rat model, which was applied to cape pertussis-induced HFS pathogenesis and prevention and treatment research. Methods A total of 115 SD female rats were divided into groups A, B, C, D, E and F according to the experimental requirements. Group A was treated with capecitabine 200mg / kg for 7 days, twice a day for 3 days. Group B was fed with Capecitabine on the basis of group A again for 7 days. The rats in group C were treated with 400mg / kg C for 7d and 2 times per day. D, E group as blank control group, F group as normal control group. The established HFS model was compared by image comparison, HE staining and Sirius red staining. Results The incidence of HFS in group A was 40.0%, the total incidence in group B was 77.5%, the incidence of HFS in group C was 80.0%, and the incidence of HFS in groups D, E and F was all 0. The statistical analysis showed that there was significant difference in the incidence of HFS between group A and group B and C (P <0.001). There was no significant difference in the incidence of HFS between group B and group C (P = 1.000). However, mean body mass (F = 6.779 3, P <0.001) and mean body mass in the second cycle (F = 23.611 1, P <0.001) of the first cycle in group C were significantly lower than those in group B. Conclusions Compared with 200 mg / kg Capecitabine administered intragastrically for 2 cycles, Capecitabine 200 mg / kg given orally for one cycle has a lower incidence of HFS while 400 mg / kg Capecitabine Coastal stomach administration of two cycles, and can not increase the success rate of modeling, but also increased the cost of modeling, causing increased adverse reactions. Therefore, 200mg / kg capecitabine intragastric administration of two cycles of modeling methods, without increasing the cost of modeling at the same time, both to ensure a high success rate of modeling (77.5%), it will not cause large model Rats developed severe adverse drug reactions and were able to establish a rat model of high quality capecitabine-induced HFS.