培美曲塞腹腔用药对H22腹水瘤小鼠腹水抑制作用的实验研究  

Intraperitoneal perfusion of pemetrexed on malignant ascites of H22 ascites-bearing mice model

作　　者：李永强[1] 潘琦津[1] 胡晓桦[1] 刘志辉[1] 廖小莉[1] 林燕[1] 

机构地区：[1]广西医科大学附属肿瘤医院化疗一科,广西南宁530021

出　　处：《中华肿瘤防治杂志》2012年第23期1780-1784,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：广西卫生厅重点科研课题(重200869)

摘　　要：目的:探讨培美曲塞腹腔用药对荷H22肝癌腹水瘤昆明小鼠的疗效与安全性。方法:制备恶性腹水模型,造模24h后随机分为空白对照组(生理盐水)和培美曲塞低、中、高剂量组〔10、50和90 mg/(kg.d)〕以及顺铂组〔0.6mg/(kg.d)〕5组,每组18只。分组后给予各药物连续10d腹腔内注射治疗。每天用药前测量小鼠的体质量、腹围,并观察小鼠日常活动状态。用药结束24h后(第11天)各组处死8只小鼠测量腹水量,并解剖小鼠观察腹腔脏器及肺脏的转移情况。流式细胞仪检测腹水中H22细胞凋亡率。其余剩下小鼠观察其生存时间,计算生命延长率。结果:培美曲塞腹腔用药可改善荷瘤小鼠生存质量。培美曲塞低、中、高剂量组及顺铂组小鼠腹水量分别为(15.05±3.95)、(10.93±3.05)、(8.08±2.22)和(7.30±2.32)mL,较空白对照组(17.85±2.56)mL减少,其中培美曲塞中、高剂量组及顺铂组与空白对照组比较,差异有统计学意义,P<0.01。培美曲塞腹腔用药可减少荷瘤小鼠脏器转移。培美曲塞低、中、高剂量组及顺铂组小鼠平均生存时间分别为(14.30±2.26)、(15.70±1.89)、(20.10±5.90)及(19.1±3.21)d,较空白对照组(13.20±1.93)d有不同程度延长,生命延长率分别为8.33%、18.94%、52.27%和44.70%,其中培美曲塞中、高剂量组及顺铂组与空白对照组相比,小鼠生命延长差异有统计学意义,P<0.01。培美曲塞低、中、高剂量组和顺铂组小鼠腹水中H22细胞凋亡率分别为(1.81±0.76)%、(3.63±1.19)%、(8.85±1.86)%和(7.68±2.17)%,均高于空白对照组的(0.73±0.23)%,差异均有统计学意义,P<0.01。结论:培美曲塞腹腔用药治疗荷H22腹水瘤具有较好的疗效,并且在补给叶酸后安全性好,其机制可能与培美曲塞诱导鼠肝癌H22细胞凋亡相关。OBJECTIVE：To evaluate the effect and safety of intraperitoneal administration of pemetrexed on H22 as cites -bearing mice. METHODS：Mice model of ascites were established and divided into 5 groups （18 per group）at random after 24 h inoculation ： normal control group （normal saline） ; pemetrexed low, middle, high dose group [pemetrexed 10,50, 90 mg/（kg · d）]; cisplatin group [DDP,0.6 mg/（kg · d）]. Mice were treated with i. p. injection of each drug on day 1- 10 day （i. p. ,qd× 10）. The bodyweights,abdomen circumference and behavior of the mice were measured every day be fore treatment. Eight mice of each group were sacrificed and surveyed ascites volumes on the llth day. Also, H22 cells in ascites were checked the apoptosis rates by flow cytometry. The rest mice were checked the survival days,and calculated the life-prolonging rate. RESULTS： Intraperitoneal administration of pemetrexed could improve the quality of life of the H22 ascites -bearing mice. The Mean volume of ascites of PEM low,middle,high dose group,and DDP group were （15.05 ±3.95） ,（10.93±_3.05） ,（8.08±2.22） and （7.30±2.32） mL. The ascites volume were lower as compared to normal control group （17.85± 2.56） mL. Especially, the most significant were pemetrexed middle, high dose group, DDP group （P〈0.01）. Intraperitoneal administration of pemetrexed could reduce the rate of metastasis. The mean survival days of pemetrexed low, middle, high dose group, and DDP group were （14. 30 ± 2. 26）, （15. 70± 1. 89）, （20. 10 ± 5.90）and （19.1±3.21 ） d, prolonged compared with the mean survival days of the control group（13.20±1.93） d. Life-prolon- ging rate were 8.33% ,18.94G ,52.27G and 44.70G. The most significant were pemetrexed middle,high dose group, DDP group （P〈0.01）. The apoptosis rates of H22 cells in pemetrexed low,middle,high dose group,and DDP group were （1. 81±0.76）%, （3.63±1.19）%, （8.85± 1.86）% and （7.68±2.17）% ,respectively. Compared with the

关 键 词：培美曲塞 腹水 腹腔 药物疗法 疾病模型 动物 细胞凋亡 小鼠 

分 类 号：R965[医药卫生—药理学] R735.7[医药卫生—药学]