利用荷H22腹水瘤小鼠恶性腹水模型比较培美曲塞腹腔用药与静脉用药的疗效

Efficacy of intraperitoneal versus intravenous pemetrexed administration in management of malignant ascites in mice bearing ascitic hepatoma-22

目的:比较培美曲塞腹腔用药与静脉用药两种途径对荷H22腹水瘤小鼠恶性腹水的抑制作用.方法:♂昆明小鼠腹腔内注射密度为1×107/mL H22瘤细胞悬液0.2mL(含H22细胞数2×106)制备恶性腹水小鼠模型.小鼠造模为第0天,荷瘤小鼠出现腹水(第5天)后立即按体质量随机分成3组,每组18只.分别为:空白对照组(等体积生理盐水,腹腔用药)、培美曲塞腹腔用药组(培美曲塞300mg/kg,腹腔用药)、培美曲塞静脉用药组(培美曲塞300mg/kg,静脉用药),用药时间均为d5、d8.每天测量小鼠的体质量、腹围,并观察其日常生活状态,第11天处死各组8只小鼠测量腹水量.其余剩下小鼠观察其生存时间,计算生命延长率.结果:空白对照组、培美曲塞腹腔用药及静脉用药组小鼠腹水量分别为15.74mL±1.71mL、13.31mL±2.45mL、8.58mL±1.89mL.与空白对照组比较,培美曲塞用药两组小鼠腹水量均可减少(P<0.05),但培美曲塞静脉用药组小鼠腹水量明显较培美曲塞腹腔用药组减少(P<0.01).培美曲塞腹腔用药及静脉用药组小鼠平均生存时间分别为15.10d±0.46d、17.90d±0.71d,较空白对照组14.20d±0.44d延长,生命延长率分别为6.34%、26.06%.培美曲塞腹腔用药组小鼠生存时间与空白对照组无差异(P>0.05),而培美曲塞静脉用药组与空白对照组及培美曲塞腹腔用药组比较,均可明显延长小鼠生存时间(P<0.01).结论:培美曲塞腹腔用药途径治疗荷H22腹水瘤小鼠疗效并不优于传统静脉用药.

AIM：To compare the effectiveness of intraperitonea and intravenous administration of pemetrexed（PEM） in the management of malignant ascites in mice bearing hepatoma-22（H22）.METHODS：A mouse model of ascites was established by intraperitoneal injection of 0.2mL of H22 cell suspension（at a density of 1×10^7/mL cells）.The mice were randomly divided into three groups at random on day 5 after induction of ascites（n= 8 per group）：normal control group（normal saline）,intraperitoneal pemetrexed group（PEM 300mg/kg）,and intravenous pemetrexed group（PEM 300mg/kg）.Pemetrexed was injected intraperitoneally or intravenously on days 5 and 8.The body weight,abdomen circumference and behavior of the mice were measured daily.Eight mice of each group were sacrificed on day 11 to measure the volume of ascites.The survival time of rest mice were recorded.RESULTS：The mean volumes of ascites in the normal control group,intraperitoneal pemetrexed group and intravenous pemetrexed group were 15.74mL±1.71mL,13.31mL±2.45mL and 8.58mL±1.89mL,respectively.In comparison to the normal control group,the two pemetrexed treatment group had significantly less production of ascites in（both P0.05）.The mean volume of ascites in the intraperitoneal pemetrexed group was significantly lower than that in the intravenous administration group（P 0.01）.The mean survival times of mice in the intraperitoneal pemetrexed group,intravenous pemetrexed group,and normal control group were 15.10d±0.46d,17.90d±0.71d,and 14.20d±0.44d,respectively.The survival time was prolonged by 6.34% and 26.06% in the intraperitoneal pemetrexed group and intravenous pemetrexed group compared to the normal control group.There was no significant difference in the survival time between the intraperitoneal pemetrexed group and normal control group（P0.05）,but the mean survival time was significantly longer in the intravenous pemetrexed group than in the normal control group and intraperitoneal pemetrexed group（both P0.01）.CONCLUSION：Intraperitoneal administration of pemetrexed is not superior to traditional intravenous administration in the management of malignant ascites in mice bearing ascitic hepatoma-22.