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蒿甲醚自微乳化给药系统对小鼠人脑胶质瘤皮下移植瘤的抑瘤

作用研究 Δ

张亚红 ，王丽娟，林凤云，兰作平，甘淋玲（重庆医药高等专科学校药学院/重庆市药物制剂工程技术研究中心，
#
＊
重庆 401331）

中图分类号 R947；R285 文献标志码 A 文章编号 1001-0408（2020）04-0464-04
DOI 10.6039/j.issn.1001-0408.2020.04.14

摘 要 目的：研究蒿甲醚（ARM）自微乳化给药系统（SMEDDS）对人脑胶质瘤皮下移植瘤模型小鼠的抑瘤效果。方法：以人脑
胶质细胞瘤细胞株SHG44接种，并以组织块移植传代，建立裸小鼠皮下移植瘤模型。分别于接种后的第5、10、15、20、25天时测量
小鼠肿瘤组织体积，绘制肿瘤生长曲线，确定肿瘤快速增殖初期。取裸小鼠30只，同法建立皮下移植瘤模型，并于肿瘤快速增殖
初期时分为对照组（生理盐水）、ARM混悬液组[60 mg/（kg·d）]和ARM-SMEDDS低、中、高剂量组[10、20、30 mg/（kg·d）]并灌胃给
予生理盐水或相应药液，每日1次，连续给药30 d。记录小鼠体质量变化及一般情况，测定肿瘤组织体积变化并计算相对肿瘤增
殖率。结果：皮下移植肿瘤块组织后第10天左右即进入肿瘤快速增殖初期。给药期间各组小鼠一般情况正常，未见明显异常反
应。自给药第 10 天起，ARM-SMEDDS 各剂量组小鼠的肿瘤组织体积均较对照组显著缩小（P＜0.05）；自给药第 15 天起，
ARM-SMEDDS各剂量组小鼠的肿瘤组织体积均较ARM混悬液组显著缩小（P＜0.05）。末次给药后，ARM-SMEDDS各剂量组小
鼠的相对肿瘤增殖率均较ARM混悬液组均显著降低（P＜0.05）。结论：ARM-SMEDDS具有明显的抑制人脑胶质瘤增长的效果，
抑瘤效果优于剂量更高的ARM混悬液剂型。
关键词 蒿甲醚；自微乳化给药系统；人脑胶质瘤细胞；皮下移植瘤；小鼠；抑瘤作用
Study on Anti-tumor Effects of Artemether Self-microemulsifying Drug Delivery System on Subcutaneous
Transplantation of Human Glioma in Mice
ZHANG Yahong，WANG Lijuan，LIN Fengyun，LAN Zuoping，GAN Linling（School of Pharmacy，Chongqing
Medical and Pharmaceutical College & Chongqing Engineering Research Center of Pharmaceutical Sciences，
Chongqing 401331，China）

ABSTRACT OBJECTIVE：To study the anti-tumor effect of artemether （ARM） self-microemulsifying drug delivery system
（SMEDDS） on human glioma subcutaneously transplanted model mice. METHODS： Human glioma cell line SHG44 was
inoculated and passed on to establish subcutaneous transplanted tumor model of nude mice. At the 5th，10th，15th，20th and 25th
day after inoculation，the tumor tissue volume was measured and the growth curve was drawn to confirm the initial stage of rapid
tumor proliferation. Thirty nude mice was collected to establish subeutaneously transplanted tumor nude model，and then divided
into control group （normal saline），ARM suspension group [60 mg/（kg·d）]，ARM-SMEDDS low-dose，medium-dose and
high-dose groups [10，20，30 mg/（kg·d）] at the initial stage of rapid tumor proliferation. They were given normal saline and
relevant solution intragastrically once a day，for consecutive 30 d. The weight change and general sibuation of mice were recorded.
The change of tumor volume was determined and relative tumor proliferation rate was calculated. RESULTS：The subcutaneously
transplanted tumor tissue entered the initial stage of rapid tumor proliferation from the 10th day after transplantation. The general
situation was normal，and there was no obvious abnormal reaction in mice of each group during treatment. Since 10th day of
administration，tumor tissue volume of mice in ARM-SMEDDS groups were shortened significantly than control group（P＜0.05）.
At 15th day of administration，tumor volume of mice in ARM-SMEDDS groups were shortened significantly than ARM suspension
group（P＜0.05）. After last administration，relative tumor proliferation rates of mice in ARM-SMEDDS groups were decreased
significantly，compared with ARM suspension group （P＜0.05）. CONCLUSIONS：ARM-SMEDDS show significant inhibitory
effect on the proliferation of human glioma，and are better than suspension with higher dosage.
KEYWORDS Artemether；Self-microemulsifying drug delivery system；Human glioma cells；Subcutaneous transplanted tumor；
Mice；Anti-tumor effect

Δ 基 金 项 目 ：重 庆 市 卫 生 健 康 委 中 医 药 科 技 项 目（No.
脑胶质瘤是中枢神经系统最常见的颅内恶性肿瘤，
ZY201703070）
每 10 万人中约有 10～20 人患病，其发病率约占恶性肿
＊副教授，硕士。研究方向：药物新剂型、药物分析。电话：023-
瘤的 1％～3％；在所有胶质细胞瘤患者中，胶质母细胞
61969189。E-mail：ya1234001@126.com [1]
# 通信作者：副教授，博士研究生。研究方向：抗肿瘤新药。电 瘤患者 1 年生存率约为 30％，但 5 年生存率不足 5％ 。
话：023-61969189。E-mail：365620247@qq.com 目前，手术、放射和药物治疗等仍是脑胶质瘤最主要的

·464 · China Pharmacy 2020 Vol. 31 No. 4 中国药房 2020年第31卷第4期