牛蒡子苷元对小鼠和大鼠抗肿瘤免疫增强作用研究

中国药物警戒 ›› 2017, Vol. 14 ›› Issue (7): 389-393.

牛蒡子苷元对小鼠和大鼠抗肿瘤免疫增强作用研究

李涛¹, 程国良², 董方², 李敏¹, 王平平¹, 姚景春^1*

1 鲁南制药集团股份有限公司新药药理中心/中药制药共性技术国家重点实验室/临沂市天然药物免疫药理毒理企业重点实验室,山东临沂 276000;
2 鲁南制药集团股份有限公司医学部,山东临沂 276000

收稿日期:2017-08-16 修回日期:2017-08-16 出版日期:2017-07-20 发布日期:2017-08-16
通讯作者: 姚景春,男,硕士,高级工程师,新药药理毒理研究。E-mail:yaojingchun@lunan.cn
作者简介:李涛,男,本科,新药药理毒理研究。
基金资助:
2015年山东省自主创新及成果转化专项（2015ZDJQ05004）：牛蒡子苷元及其衍生物（IDO抑制剂）的研究与开发

Study on Enhancement of Murine and Rat Anti-tumor Immunity Induced by Arctigenin

LI Tao¹, CHENG Guo-liang², DONG Fang LI Min¹, WANG Ping-ping¹, YAO Jing-chun^1,*

1 Center for New Drug Pharmacology of Lunan Pharmaceutical Group Co.Ltd/State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine/Linyi Key Laboratory for Immunopharmacology and Immunotoxicology of Natural Medicine, Shandong Linyi 276000, China;
2 Medical Department of Lunan Pharmaceutical Group Co.Ltd, Shandong Linyi 276000, China

Received:2017-08-16 Revised:2017-08-16 Online:2017-07-20 Published:2017-08-16

摘要/Abstract

摘要： 目的肿瘤免疫干预活性药物的筛选尚无功能评价方法,探索使用SD大鼠和ICR小鼠建立对人源瘤株抗肿瘤免疫的评价方法,考察牛蒡子苷元对机体抗肿瘤免疫增强作用。方法大鼠皮下注射给予牛蒡子苷元,同时用人源肿瘤细胞对大鼠免疫,分离大鼠白细胞、血清并与人源肿瘤细胞共培养,检测培养上清液中乳酸脱氢酶（lactate dehydrogenase,LDH）的含量,考察大鼠白细胞与免疫血清对人源瘤株的杀伤力;应用冻融法制备H₂₂细胞裂解物H₂₂TCL。ICR小鼠给药第1、4和7天H₂₂TCL腹腔免疫,第11天小鼠停药并接种H₂₂细胞于腋下,观察肿瘤的发生率,验证牛蒡子苷元抗肿瘤免疫增强作用。结果牛蒡子苷元能够增强SD大鼠白细胞、血清与人源肿瘤细胞体外共培养上清液中LDH含量;牛蒡子苷元能够显著降低ICR小鼠肿瘤的发生率。结论本研究建立使用SD大鼠的免疫血清、白细胞与肿瘤细胞共培养,检测上清中LDH含量筛选抗肿瘤免疫药物的方法,并且牛蒡子苷元降低了小鼠肿瘤的发生率,从而证实了牛蒡子苷元影响了机体的免疫系统,提高动物的抗肿瘤免疫能力,牛蒡子苷元能够提高机体免疫系统对肿瘤细胞的杀伤作用,提高机体抗肿瘤免疫力。

关键词: 牛蒡子苷元, 抗肿瘤免疫, 人参皂苷Rg₃, 乳酸脱氢酶, 免疫血清, 白细胞

Abstract: Objective To explore a new method evaluating the anti-tumor immunological effects of arctigenin in SD rats and ICR mice. Methods SD rats were treated with arctigenin subcutaneously. Simultaneously, the rats were immunized with human tumor cells by intraperitoneal injection every 3 days. Immunized for 3 times, rats were kept on treating with arctigenin for another week. Then after 4 days, white cells and serum of rats were harvested and co-cultured with human tumor cells. Content of lactic dehydrogenase in the supernatant was detected. H₂₂TCL was prepared from H₂₂ melanoma cells by freezing-thaw. ICR mice were randomly divided into 6 groups and administrated with arctigenin for 10 days. On day 1、4 and 7, mice were injected intraperitoneally with H₂₂TCL. On day 10, H₂₂ cells were injected to the right flank of mice. On the twentieth day, the incidence of tumor in mice were monitored. Results Arctigenin and ginsenoside Rg3 can enhance LDH releasing. Arctigenin can reduce the incidence of mice bearing H₂₂ tumor. Conclusion We explore a new simple way to evaluate effects of antitumor drugs on immune system, and arctiin reduced the incidence of tumor in mice, thus confirming the effects of arctiene aglycone on the body's immune system and improving the animal's anti-tumor immunity; arctigenin can improve the immune response to suppress tumor cells.

Key words: arctigenin, anti tumor immunity, ginsenoside Rg₃, lactate dehydrogenase, immune serum, white cells

中图分类号:

R965

李涛, 程国良, 董方, 李敏, 王平平, 姚景春. 牛蒡子苷元对小鼠和大鼠抗肿瘤免疫增强作用研究[J]. 中国药物警戒, 2017, 14(7): 389-393.

LI Tao, CHENG Guo-liang, DONG Fang LI Min, WANG Ping-ping, YAO Jing-chun. Study on Enhancement of Murine and Rat Anti-tumor Immunity Induced by Arctigenin[J]. Chinese Journal of Pharmacovigilance, 2017, 14(7): 389-393.

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