目的 探討吉非替尼按時辰給藥荷瘤小鼠的藥效學(xué)特點。方法 利用C57BL/6小鼠建立Lewis肺癌小鼠模型，將荷瘤小鼠隨機分成7組，每組8只，分別為對照組，8：00、12：00、16：00、20：00、24：00和次日4：00時給藥的實驗組（A、B、C、D、E、F組）。ig給藥50 mg/kg，對照組給予相同劑量含有羧甲基纖維素鈉的蒸餾水。每天觀察小鼠的生存質(zhì)量和肛周紅腫的數(shù)量；每3天測定小鼠腫瘤的直徑，計算小鼠的腫瘤體積。經(jīng)過3周的給藥，小鼠進行眼眶取血，處死小鼠并剝離腫瘤，稱定質(zhì)量，計算抑瘤率。取部分腫瘤組織做病理切片，觀察腫瘤組織壞死情況；同時取小鼠皮膚組織進行掃描電鏡觀察。運用ELISA技術(shù)檢測血液中IL-6的水平。結(jié)果 吉非替尼可以明顯地抑制荷瘤小鼠腫瘤的生長。與其他實驗組比較，A組（8：00時給藥）小鼠腫瘤體積增長最緩慢，其抑瘤率最高，F(xiàn)組（次日4：00給藥）次之。病理學(xué)分析顯示A組（8：00時給藥）的腫瘤組織壞死情況最嚴(yán)重。通過掃描電鏡觀察上皮細(xì)胞發(fā)現(xiàn)，A組（8：00時給藥）和F組（次日4：00時給藥）的上皮細(xì)胞損傷較輕，其肛周紅腫發(fā)生率和IL-6水平較其他實驗組低。結(jié)論 吉非替尼對荷瘤小鼠的抗腫瘤作用和毒副作用存在一定的時辰節(jié)律性，8：00和4：00時療效較好。

Objective To compare the efficacy and adverse effects of gefitinib administration at different time points during a day on Lewis lung carcinoma in tumor-bearing mice. Methods The Lewis lung carcinoma model was built in C57BL/6 mice. The animals were randomly divided into seven groups (n=8), including control and A-F six experimental groups which were treated at 8:00, 12:00, 16:00, 20:00, 24:00, and the next day 4:00. Mice in the six experimental groups were ig given a single dose of gefitinib (50 mg/kg), and those in the control group were provided with distilled water containing sodium carboxymethylcellulose daily. The quality of life and perianal swelling was recorded every day, and the tumor volume was determined every three days. After three weeks of the administration of gefitinib to the mice, the tumor inhibition rate was calculated and some tumors were used for pathological analysis. And some skin tissues were sent to inspect by scanning electron microscope (SEM). The blood samples were collected for ELISA. Results Gefitinib could significantly inhibit the growth of tumor in C57BL/6 mice. The tumor volume of group A (administrated at 8:00) increased more slowly (P< 0.01), with the maximum tumor inhibition rate. Group F (administrated at the next day 4:00) took the second place. Histological analysis showed that tumor tissue necrosis in A group (administered at 8:00) was the severest. And SEM analysis showed less injury to the skin tissue when gefitinib was administered at 8:00 and the next day 4:00. The perianal smelling rate and IL-6 levels in A and F groups were lower than others. Conclusion Both the anti-tumor effect and toxicities of gefitinib display circadian rhythm. Administration at 8:00 and 4:00 can impove its efficacy.