高脂血症对结直肠癌模型化疗作用影响的实验研究  

Experimental study of the impact of hyperlipidemia on the chemotherapy in colorectal cancer model

作　　者：何勇山[1] 金黑鹰[2] 章金春[3] 周阿成[1] 

机构地区：[1]南京中医药大学研究生院,210001 [2]南京中医药大学附属第三医院全国肛肠诊疗中心 [3]南京中医药大学附属第三医院检验科

出　　处：《中华胃肠外科杂志》2013年第6期583-587,共5页Chinese Journal of Gastrointestinal Surgery

基　　金：国家自然科学基金（30572447,30973837）

摘　　要：目的研究高脂血症对结直肠癌模型化学治疗的影响。方法通过高脂饮食喂养及肿瘤移植建立高脂血症结肠皮下易位结肠癌原位移植模型。将70只裸鼠分为7组，每组10只，其中有两组为预实验组，另外5组中有4组为高脂饮食组（G1～G4），1组为对照组（G5）予以常规饮食。G1组给予生理盐水，G2-G5分别给予卡培他滨和辛伐他汀处理3周，观察5组裸鼠肿瘤的体积、体质量和增长率以及血脂指标（TC、TG、HDL、LDL、Lpa、apoA、apoB）。结果G1～G4组TC、HDL和apoA升高，与喂养前相比，差异有统计学意义（分别为P〈0．05和P〈0．01），而TG、LDL、Lpa和apoB有增高趋势，但与喂养前相比差异无统计学意义（均P〉0．05）。G1组在各时间点肿瘤体积增长率均超过其他各组，除G3组（P〉0．05）外，差异均具有统计学意义（分别为P〈0．01和P〈0．05）；单纯使用辛伐他汀治疗的G3组肿瘤增长率低于G1组，但是高于G2、G4和G5组，差异有统计学意义（分别为P〈0．01和P〈0．05）；G5组肿瘤生长高于G2和G4组，差异无统计学意义（P〉0．05）；使用卡培他滨合并辛伐他汀处理的G4组肿瘤生长最慢，略低于单纯使用卡培他滨处理的G2组，但差异无统计学意义（P〉0．05）；与预实验组血脂结果相比，在给药治疗的第3周，G1组的Tc升高[（3．8±0．4）mmol／L1，而其他4组TC降低[G2组（2．8±1．8）mmol／L；G3组（2．9±0．7）mmol／L：G4组（1．4±0．9）mmol／L；G5组（2．1±0．2）mmol／L]，以使用卡培他滨联合辛伐他汀的G4组降低最为明显（P=0．004）；第5周Tc均出现下降趋势，但是G4和G5组Tc高于第3周；G1～G4组TG、Lpa和apoA在第3周均出现下降（分别为TG：P〈0．01和P〈0．05；Lpa：P〈0．05和P〈0．01；apoA：P〈0．05和P〈0．01）；Gl～G5组HDL和apoB第3周与第5周检测结果差异无统计学意义（均P〉0．05）。结论Objective To study the effect of hyperlipidemia on the prognosis and therapeutic response for colorectal cancer and to explore the associated mechanism. Methods The hyperlipidemic subcutaneous heterotopic colorectal cancer orthotopic transplant model of nude mice was established by feeding high fat diet and performing transplantation. Seventy mice were divided into 7 groups with 10 mice in each group. Two groups were used as pre-experiment. The remaining 5 groups included 4 highfat groups （G1 to G4）, and 1 normal-diet control group （GS）. G1, G2, G3, G4, and G5 received normal saline, capecitabine, simvastatin, capecitabine plus simvastatin and capecitabine respectively for 3 weeks. Changes of tumor volume, tumor weight, tumor growth rate and blood lipid parameters （TC, TG, HDL, LDL, Lpa, apoA and apoB） were observed. Results In G1 to G4, TC, HDL, apoA, TG, LDL, Lpa, apoB increased, but only TC, HDL, apoA were significantly different as compared with G5 （P=0.020, P=0.001, P=0.001, P=0.911, P=0.249, P=0.681, P=0.053）. The tumor in G1 grew fastest, and its growth rate was significantly different as compared witfi G2, G4, G5 except G3 （P=0.001, P=0.806, P=0.001, P=0.010）. The tumor growth rate of G3 was lower than group G1, but higher than G2, G4, G5 with significant difference （P=0.001, P=0.002, P=0.016）. The tumor of G5 grew faster than G2 and G4, but without significant differences （P=0.051, P=0.070）. The tumor of G4 grew slowest without significant difference as compared to G2 （P=0.438）. Compared with preadministration, at the third week, the TC of G1 was increased [ （3.8±0.4） mmol/L1, while the other 4 groups decreased[G2 （2.8±1.8） mmol/L, G3（2.9±0.7） mmol/L, G4（1.4±0.9） mmol/L, G5（2.1±0.2） mmol/L]. G4 decreased significantly （P=0.004）. At the fifth week, the TC of all the 5 groups decreased, while the lipids of G4 were higher as compared to those at the third week. The TG, Lpa, ApoA were significantly decreased at the third week （all P〈0.05 ）, w

关 键 词：结直肠肿瘤 高脂血症 卡培他滨 辛伐他汀 裸鼠 

分 类 号：R735[医药卫生—肿瘤] R-332[医药卫生—临床医学] R589