多烯磷脂酰胆碱对奥沙利铂联合氟尿嘧啶所致荷瘤裸鼠肝损伤的保护作用

Effects of Polyene Phosphatidylcholine on Hepatic Injury of Tumor-bearing Nude Mice Induced by Oxaliplatin and 5-fluorouracil Chemotherapy

目的探讨多烯磷脂酰胆碱对奥沙利铂联合氟尿嘧啶所致肝损伤的保护作用。方法 30只BALB/c裸鼠皮下种植结肠癌HCT116细胞制备荷瘤裸鼠模型,随机分为3组:肝损伤组,实验首日腹腔注射奥沙利铂(6 mg·kg^(-1)·d^(-1))0.2 mL,同时连续7 d腹腔注射氟尿嘧啶(20 mg·kg^(-1)·d^(-1));多烯磷脂酰胆碱组,在给予等量氟尿嘧啶和奥沙利铂前30 min,腹腔注射多烯磷脂酰胆碱(85 mg·kg^(-1)·d^(-1))0.2 mL,共7 d;荷瘤空白组,注射生理盐水作为对照。取各组裸鼠肝脏,石蜡切片,HE染色,光学显微镜下观察肝脏组织的变化;制作超薄切片,电子显微镜下观察肝细胞超微结构的变化;制作10%肝组织匀浆,黄嘌呤氧化酶法检测肝组织超氧化物歧化酶(SOD)活性,比色法检测过氧化氢酶(CAT)活性。结果肝损伤组裸鼠肝脏的胞质局部溶解,线粒体膜破损,细胞核膜水肿模糊,肝窦扩张,多烯磷脂酰胆碱部分逆转了这些损伤。与荷瘤空白组相比,肝损伤组SOD和CAT的表达明显降低(P<0.05);与肝损伤组相比,多烯磷脂酰胆碱组SOD和CAT的表达升高(P<0.05)。说明多烯磷脂酰胆碱能减轻化疗药物对肝脏的毒性作用,抑制氧化应激反应。结论多烯磷脂酰胆碱对氟尿嘧啶联合奥沙利铂引起的肝损伤具有预防、保护作用,该作用可能与其膜修复和抗氧化应激反应的作用有关。

Objective To study the protective effect of polyene phosphatidylcholine on hepatic injmy induced by oxaliplatin and 5-fluorouracil. Methods A subcutaneous tumor model was estabhshed by transplanting colocareinoma HCT116 cells into 30 nude mice, which were randomized into three groups. The polyene phosphatidylcholine group was injected with polyene phosphatidylcholine （ 85 mg·kg^-1·d^-1） and 5-fluoroumcil （20 mg·kg^-1·d^-1 ） for 7 days, and then injected with oxaliplatin （6 mg·kg^-1·d^-1） for 1 day. The hepatic injury group was injected with 5-fluorouracil （20 mg·kg^-1·d^-1） for 7 days and oxaliplatin （6mg·kg^-1·d^-1） for 1 day. The tumor-bearing blank group was injected with normal saline. Hepatic injury was observed with uhrathin pathological sections. Liver homogenates were prepared to detect superoxide dismutase （SOD） and catalase （CAT） activity. Results In the hepatic injury group, pathological sections revealed dissolved cellular cytoplasm, mitochondrial membrane damage, cell membrane edema, and fuzzy, sinusoidal cell expansion. There were no obvious hepatic injuries observed in the polyene phosphatidylcholine group. The expression of SOD and CAT were lower in the hepatic injury and polyene phosphatidylcholine groups compared to the tumor-bearing blank group （ P 〈 0.05）. The expression of SOD and CAT were higher in the polyene phosphatidylchohne group compared to the hepatic injury group （P 〈 0.05 ）. Conclusion Polyene phosphatidylchohne has a protective effect on hepatic injury induced by oxaliplatin and 5-fluorouracil, which may be related to its effect on membrane repair and inhibition of oxidative stress.