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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

发布时间:2018-12-10 21:01
【摘要】: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(P0.05);与肝损伤组相比,多烯磷脂酰胆碱组SOD和CAT的表达升高(P0.05)。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。
[Abstract]:Objective to investigate the protective effect of polyene phosphatidylcholine on liver injury induced by oxaliplatin and fluorouracil. Methods Thirty nude BALB/c nude mice with colon cancer HCT116 cells implanted subcutaneously were randomly divided into 3 groups: liver injury group. On the first day of the experiment, oxaliplatin (6 mg kg~ (-1) d ~ (-1) 0.2 mL,) was injected intraperitoneally. Fluorouracil (20 mg kg~ (-1) d ~ (-1);) was injected intraperitoneally for 7 days at the same time. In the polyenylphosphatidylcholine group, intraperitoneal injection of polyenylphosphatidylcholine (85 mg kg~ (-1) d-1) 0.2 mL, for 7 days was performed 30 min, before the same dose of fluorouracil and oxaliplatin. The control group was injected with normal saline. The liver, paraffin sections, HE staining and optical microscope were used to observe the changes of liver tissue, ultrathin sections and ultrastructure of hepatocytes were observed under electron microscope. The activity of superoxide dismutase (SOD) was detected by xanthine oxidase method and the activity of catalase (CAT) was detected by colorimetry. Results in the liver injury group, the cytoplasm of the liver was partially dissolved, the mitochondria membrane was damaged, the nuclear membrane edema was blurred, the hepatic sinusoid dilated, and the damage was partially reversed by polyenylphosphatidylcholine. Compared with the control group, the expression of SOD and CAT in liver injury group was significantly lower (P0.05); compared with liver injury group, the expression of SOD and CAT in polyene phosphatidylcholine group was higher than that in liver injury group (P0.05). The results showed that Polyene phosphatidylcholine could reduce the toxic effect of chemotherapeutic drugs on liver and inhibit oxidative stress reaction. Conclusion Polyene phosphatidylcholine can prevent and protect liver injury induced by fluorouracil and oxaliplatin, which may be related to membrane repair and antioxidant stress response.
【作者单位】: 中国医科大学附属盛京医院肿瘤科;
【基金】:沈阳市科学技术计划(F13-316-1-69)
【分类号】:R735.34

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