十枣汤急性毒性及抗肿瘤疗效评价
Assessment of acute toxicity and antitumor efficacy of Shizao decoction
马立威 1陈哲 2施国善 3王玉静 4陈颂 4倪世宇 5李京 6葛鹏玲 7刘吉成8
作者信息
- 1. 齐齐哈尔医学院医药科学研究所(博士后工作站),黑龙江齐齐哈尔 161006;黑龙江中医药大学博士后流动站,黑龙江哈尔滨 150040
- 2. 齐齐哈尔医学院公共卫生学院,黑龙江齐齐哈尔 161006
- 3. 贵州中医药大学基础医学院,贵州贵阳 550025
- 4. 齐齐哈尔医学院药学院,黑龙江齐齐哈尔 161006
- 5. 齐齐哈尔医学院附属第五医院,黑龙江 大庆 163001
- 6. 齐齐哈尔医学院附属第三医院,黑龙江齐齐哈尔 161099
- 7. 黑龙江中医药大学博士后流动站,黑龙江哈尔滨 150040
- 8. 齐齐哈尔医学院医药科学研究所(博士后工作站),黑龙江齐齐哈尔 161006
- 折叠
摘要
本研究旨在评价十枣汤(SZD)对KM小鼠的急性毒性及抗肿瘤活性,为安全用药提供参考,并对抗肿瘤效应进行初步评价.试验中,SPF级KM小鼠分别ig给予一定量的生理盐水(空白对照)和SZD,测定其半数致死量(LD50),评价其对小鼠的毒性.另选取SPF级SD大鼠,ig给予SZD,制备SZD含药学清(MS);MTT法、乳酸脱氢酶(LDH)活力检测,甲基纤维素克隆形成实验,流式细胞术等检测SZD-MS对肿瘤细胞增殖抑制及诱导凋亡情况.毒性测试结果显示,小鼠无死亡,无法得出SZD的LD50.与空白对照组比较,血液的生化学指标显示,差异有统计学意义(P＜0.05,P＜0.01);H&E检测结果显示,SZD对小鼠的肝、肾功能有一定的损伤.抗肿瘤作用结果显示:与溶剂对照组比较,SZD-MS对5种肿瘤细胞的增殖均有一定的抑制作用(P＜0.05,P＜0.01);SZD-MS对H22细胞LDH释放增加(P＜0.05);细胞克隆的形成力度下降(P＜0.05,P＜0.01);细胞的凋亡率增加(P＜0.01).研究表明,SZD经口最大给药量为每只小鼠0.8 mL/d,约相当于成人日剂量的120倍,毒性较小,安全性良好;且有较好的抗腹水瘤活性.
Abstract
This study aimed to assess the acute toxicity of Shizao decoction(SZD)in KM mice and its antitumor activity,offering insights into drug safety and antitumor efficacy.In experiments,specific pathogen-free(SPF)KM mice were administered either saline(as a blank control)or SZD,and the half-lethal dose(LD50)was determined.Additionally,SPF-grade SD rats were treated with SZD to produce SZD-medicated serum(SZD-MS).Assays,including the MTT method,lactic dehydrogenase(LDH)release,colony formation,and flow cytometry,were utilized to measure the inhibitory effects on cancer cell proliferation and induction of apoptosis.The toxicity tests revealed that none of the mice died after oral administration of SZD,rendering it impossible to establish an LD50 value.Notably,serum biochemistry results significantly diverged from those of the blank control group(P＜0.05).Histopathology,using hematoxylin and eosin(H&E)staining,unveiled that SZD exerted detectable damage on the liver and kidneys of the mice.In terms of antitumor activity,SZD-MS demonstrated a significant inhibition of proliferation in five tumor cell lines when compared to the vehicle control(P＜0.05,P＜0.01).This finding was further supported by the increased LDH release from H22 cells(P＜0.05),a reduction in colony formation(P＜0.05,P＜0.01),and an elevated apoptosis rate(P＜0.01).In conclusion,the study revealed that the maximum oral dosage of SZD,set at 0.8 mL/d for each mouse(roughly 120 times the standard adult daily dose),presented minimal toxicity.Moreover,it possessed promising anti-ascite tumor activity,suggesting its safety and therapeutic potential.
关键词
十枣汤/急性毒性/增殖抑制/抗肿瘤活性Key words
Shizao decoction/Acute toxicity/Proliferation inhibition/Antitumor activity引用本文复制引用
基金项目
National Natural Science Foundation of China(82174207)
Science and Technology Project of Guizhou Province(Qiankehe Foundation-ZK[2021]General 502)
Growth Project of Young Scientific and Tecmological Talents in General Colleges and Universities in Guizhou Province(Qianjiaohe KY[2021]208)
Qiqihar Science and Technology Bureau Joint Guide Project(LHYD-202028)
出版年
2024
NETL
NSTL
万方数据