动脉灌注化疗对大鼠脑胶质瘤的治疗作用及其机制

doi:10.13481/j.1671-587x.20150224

吉林大学学报(医学版) ›› 2015, Vol. 41 ›› Issue (02): 327-332.doi: 10.13481/j.1671-587x.20150224

动脉灌注化疗对大鼠脑胶质瘤的治疗作用及其机制

王昆鹏^1,2, 赵文清^2,3, 王维兴¹, 呼铁民¹, 康进生³, 孙鑫⁴, 鞠智卿⁵

1. 承德医学院附属医院神经外科, 河北承德 067000;
2. 河北医科大学研究生院, 河北石家庄 050017;
3. 河北省人民医院神经外科, 河北石家庄 050051;
4. 围场满族蒙古族自治县县医院神经外科, 河北承德 068450;
5. 承德医学院附属医院康复科, 河北承德 067000

收稿日期:2014-09-03 出版日期:2015-03-28 发布日期:2015-04-04
通讯作者: 赵文清, 主任医师, 教授, 博士研究生导师(Tel:0311-85988199, E-mail:2362571843@qq.com);孙鑫, 主治医师, 讲师(Tel:0314-7568061, E-mail:50594366@qq.com) E-mail:2362571843@qq.com;50594366@qq.com
作者简介:王昆鹏(1977-), 男, 河北省承德市人, 主治医师, 讲师, 医学硕士, 主要从事胶质瘤方面的研究。
基金资助:
河北省承德市科技局科技支撑计划项目资助课题(201422029)

Therapeutic effect of arterial infusion chemotherapy on glioma of rats and its mechanism

WANG Kunpeng^1,2, ZHAO Wenqing^2,3, WANG Weixing¹, HU Tiemin¹, KANG Jinsheng³, SUN Xin⁴, JU Zhiqing⁵

1. Department of Neurosurgery, Affiliated Hospital, Chengde Medical University, Chengde 067000, China;
2. Graduate School, Hebei Medical University, Shijiazhuang 050017, China;
3. Department of Neurosurgery, Hebei General Hospital, Shijiazhuang 050051, China;
4. Department of Neurosurgery, WeiChang Manchu-Mongolian Autonomous County Hospital, Chengde 068450, China;
5. Department of Rehabilitation, Affiliated Hospital, Chengde Medical University, Chengde 067000, China

Received:2014-09-03 Online:2015-03-28 Published:2015-04-04

摘要/Abstract

摘要：

目的:探讨动脉灌注化疗对大鼠脑胶质瘤的治疗作用及其机制,为临床应用提供依据。方法:24只脑胶质瘤模型大鼠随机分为动脉组、静脉组和对照组,每组8只,分别通过大鼠尾静脉(静脉组)及颈动脉(动脉组)给予化疗药物VM-26,对照组大鼠给予生理盐水。观察各组大鼠肿瘤体积和生存期;给予不同途径治疗1周后处死大鼠,采用PCR法观察大鼠肿瘤细胞中增殖细胞核抗原(PCNA)和拓扑异构酶Ⅱ(TOPOⅡ)mRNA的表达水平;免疫组织化学法检测大鼠肿瘤细胞中PCNA的阳性细胞数;流式细胞术检测大鼠肿瘤细胞凋亡率。结果:动脉组大鼠经治疗后肿瘤生长速度最慢,静脉组其次,对照组最快,动脉组大鼠肿瘤体积小于静脉和对照组(P<0.05),静脉组大鼠肿瘤体积小于对照组(P<0.05)。与对照组比较,动脉组和静脉组大鼠生存期延长(P<0.05);动脉组大鼠生存期长于静脉组,但组间比较差异无统计学意义(P>0.05)。动脉组大鼠肿瘤组织中PCNA及TOPOⅡ mRNA表达水平低于对照组和静脉组(P<0.05),静脉组大鼠肿瘤组织中PCNA及TOPOⅡ mRNA表达水平低于对照组(P<0.05)。动脉组大鼠肿瘤组织中PCNA阳性细胞数低于静脉组和对照组(P<0.05)。动脉组大鼠肿瘤细胞凋亡率高于静脉组和对照组(P<0.05)。结论:动脉灌注途径化疗使肿瘤细胞增殖速度减慢,肿瘤细胞凋亡明显增多,能更有效控制肿瘤生长。

关键词: 脑胶质瘤, 动脉灌注, 细胞核增殖抗原, 拓扑异构酶-Ⅱ, 细胞凋亡, 化学疗法

Abstract:

Objective To study the therapeutic effect and mechanism of arterial infusion chemotherapy on glioma of the rats,and to provide the basis for clinical application.Methods 24 rats were randomly divided into artery group,vein group,and control group; there were 8 rats in each group.The chemotherapy medicine VM-26 were injected through tail intravenous(vein group) and carotid arteries (artery group) into the rats, respectively,and the rats in control group were given normal saline. The tumor size and survival period of the rats were observed;all the rats were killed after giving different treatment for one week, and the expression levels of proliferating cell nuclear antigen(PCNA) and topoisomeraseⅡ(TOPO Ⅱ) in the tumor cells of the rats were detected by PCR method,meanwhile the number of PCNA positive cells in the tumor cells were detected by immunohistochemical method;the apoptotic rates of the tumor cells of the rats were detected by flow cytometry method.Results After treatment,the tumor growth speed of the rats in artery group was the slowest,which was followed by vein group, and the speed of the rats in control group was the fastest.The tumor size of the rats in artery group was smaller than those in vein and control groups,and the tumor size of the rats in vein group was smaller than that in control group(P<0.05).Compared with control group,the survival period of the rats in artery and vein groups were extended (P<0.05);the survival period of the rats in artery group was longer than that in vein group,but there was no statistically significant difference between two groups (P>0.05).The expression levels of PCNA and TOPO Ⅱ mRNA in the tumor tissue of the rats in artery group were lower than those in vein and control groups (P<0.05),and the expression levels of PCNA and TOPO Ⅱ in the tumor tissue of the rats in vein group were lower than those in control group (P<0.05).The number of PCNA positive cells in the tumor tissue of the the rats in artery group was lower than those in vein group and control group (P<0.05).The apoptotic rate of tumor cells of the rats in artery group was higher than those in vein group and control group(P<0.05).Conclusion The way of arterial perfusion chemotherapy could make the proliferation of tumor cells slow,and promote the apoptosis of tumor cells obviously,and can control the tumor growth more effectively.

Key words: glioma, arterial infusion, proliferating cell nuclear antigen, topoisomerase Ⅱ, apoptosis, chemotherapy

中图分类号:

R361.3

王昆鹏, 赵文清, 王维兴, 呼铁民, 康进生, 孙鑫, 鞠智卿. 动脉灌注化疗对大鼠脑胶质瘤的治疗作用及其机制[J]. 吉林大学学报(医学版), 2015, 41(02): 327-332.

WANG Kunpeng, ZHAO Wenqing, WANG Weixing, HU Tiemin, KANG Jinsheng, SUN Xin, JU Zhiqing. Therapeutic effect of arterial infusion chemotherapy on glioma of rats and its mechanism[J]. Journal of Jilin University Medicine Edition, 2015, 41(02): 327-332.

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动脉灌注化疗对大鼠脑胶质瘤的治疗作用及其机制

Therapeutic effect of arterial infusion chemotherapy on glioma of rats and its mechanism

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