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Bcl-2蛋白在肿瘤放化疗氧化损伤中的作用

秦绪军,何  伟,海春旭*   

  1. 第四军医大学预防医学院毒理学教研室,陕西省自由基生物学与医学重点实验室,第四军医大学抗氧化损伤防治研究中心,陕西  西安  710032
  • 收稿日期:2013-12-12 修回日期:2014-05-30 出版日期:2014-09-30 发布日期:2014-09-30
  • 通讯作者: 海春旭,E-mail:cx-hai@fmmu.edu.cn
  • 作者简介:秦绪军(1976- ),男,辽宁省抚顺人,博士,研究方向:线粒体活性氧与肿瘤及衰老。Tel:15291850398;E-mail:qinxujun @hotmail.com

Role of protein Bcl-2 in the oxidative injury induced by radiotherapy or chemotherapy

QIN Xu-jun,HE Wei,HAI Chun-xu*   

  1. Department of Toxicology, the Key Laboratory of Free Radical Biology and Medicine of Shaanxi Province, Center of Prevention and Treatment on Oxidative Injury, School of Preventive Medicine, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
  • Received:2013-12-12 Revised:2014-05-30 Online:2014-09-30 Published:2014-09-30

摘要:

目的: 探讨Bcl-2蛋白在肿瘤放化疗氧化损伤中的作用。方法:采用已建立的大鼠肿瘤放、化疗模型,分别设阴性对照组、模型组、单纯放(化)疗组、以及放(化)疗+抗氧化剂保护组。放疗大鼠给予肿瘤局部累计剂量47 Gy的60Co γ射线照射。化疗大鼠每两日1次给予2 mg/kg阿霉素腹腔注射化疗,连续注射8周。抗氧化剂保护组(安体欣60 mg/kg+Vit E 20 mg/kg+单宁2.5 mg/kg) 每日给予复合抗氧化剂灌胃1次,放疗实验大鼠连续给药5周,化疗实验大鼠连续给药8周。实验结束时处死实验动物,分别取放疗靶器官肝组织和化疗靶器官心肌组织,固定切片,采用免疫组化检测Bcl-2蛋白的表达,并对阳性显色进行光密度的量化分析。结果:Bcl-2蛋白在正常对照组的相应组织中均有一定程度的表达。与对照组比较,单纯放、化疗组可以显著抑制Bcl-2蛋白在相应靶器官组织中的表达(P<0.05),而给予抗氧化剂保护后Bcl-2蛋白的表达较相应单纯放、化疗组显著提高(P<0.05)。结论:Bcl-2是肿瘤放、化疗氧化损伤的一个重要靶分子,同时也是一个外源性抗氧化干预的重要靶点。

关键词: Bcl-2蛋白, 放疗, 化疗, 抗氧化剂, 靶点

Abstract:

OBJECTIVE: To evaluate role of protein Bcl-2 in the oxidative injury induced by radiotherapy or chemotherapy. METHODS:We employed the rat models for radiotherapy and chemotherapy. For each experiment,the rats were divided into four groups:control group,model group,radiotherapy or chemotherapy group,and protection group. The rats for radiotherapy experiment received local radiation of 60Co γ with the accumulative dosage of 47 Gy. The rats for chemotherapy experiment received doxorubicin (2 mg/kg) by intraperitoneal injection every two days. The protection groups received multiple antioxidants (Antitoxin 60 mg/kg+Vit E 20 mg/kg+Tannin 2.5 mg/kg) by gavage every day. These treatments lasted 5 weeks for radiotherapy experiment and 8 weeks for chemotherapy experiment. At the end of the experiments,all of the rats were sacrificed and the specific tissues were fixed to cut sections. The expression of protein Bcl-2 was measured by immunohistochemistry and the positive stainings were quantified by optical density analysis. RESULTS:There was a certain positive expression of protein Bcl-2 in the normal rats. Radiotherapy or chemotherapy treatment significantly inhibited the protein Bcl-2 expression (P<0.05),in which antioxidant supplementations showed obvious protection (P<0.05). CONCLUSION:Protein Bcl-2 was a key target of oxidative injury induced by radiotherapy and chemotherapy,as well as a potential target of antioxidant supplementation to reduce the side effects of radiotherapy and chemotherapy.

Key words: Bcl-2, radiotherapy, chemotherapy, antioxidant, target