目的 研究不同剂量的通关藤总皂苷（MTTS）联合阿霉素（DOX）对H22肝癌小鼠抗肿瘤的量效关系。方法 建立H22肝癌小鼠模型，随机分为模型组、DOX（1.5 mg·kg^-1）组、DOX（1.5 mg·kg^-1，隔天给药1次） ＋MTTS（分别设31.25、62.50、125.00、250.00、500.00 mg·kg^-1）组，每组10只，另设对照组10只。DOX给药组在肿瘤接种后次日给药，每隔1天给药1次； DOX＋ MTTS组DOX、MTTS轮流给药，每天给1种药，ip给药；对照组和模型组同法给予相同体积的0.9%氯化钠溶液，连续给药14 d。对小鼠进行一般行为观察、体质量观察、测量肿瘤体积并绘制肿瘤生长曲线；杀鼠后，取瘤组织称质量，并计算抑瘤率；取脾脏、胸腺称质量，并计算脾脏系数、胸腺系数；利用流式细胞术检测荷瘤小鼠外周血中T、B淋巴细胞、自然杀伤（NK）细胞比例；采用酶联免疫法检测血清炎症因子水平。结果 模型组小鼠生长状态最差，且毛发枯槁，没有光泽，精神状态不佳，活动减少，饮食减少；除DOX＋MTTS（500.00 mg·kg^-1）组外，联合给药组随着MTTS剂量增大，状态逐步变好，活动以及精神状态良好； DOX＋MTTS 500 mg·kg^-1组小鼠毛发枯槁，体质量与体积较其余各给药组都偏小，形态瘦弱，饮食不佳，从第7天开始出现死亡。模型组肿瘤体积快速增长，与模型组相比，DOX组和联合给药组肿瘤生长均出现明显抑制； DOX组抑瘤率69.68%，31.25、62.50、125.00、250.00、500.00 mg·kg^-1联合用药组抑瘤率分别为71.43%、75.95%、79.15%、83.38%、87.90%。与DOX组相比，MTTS协同DOX能够显著升高肿瘤小鼠脾脏指数、胸腺指数，显著增加CD4⁺T淋巴细胞亚群百分率，减少CD8⁺T淋巴细胞亚群百分率，升高CD4⁺/CD8⁺；显著升高CD19⁺CD20⁺B细胞亚群百分率、CD3^-CD16⁺NK细胞亚群的百分率；显著降低荷瘤小鼠血清炎症因子白细胞介素（IL）-6、IL-8、肿瘤坏死因子-α（TNF-α）水平。结论 250.00 mg·kg^-1 MTTS联合阿霉素的治疗效果最佳，降低H22荷瘤小鼠体内炎症因子水平更为突出。MTTS协同DOX能够抑制肿瘤生长，通过提高H22肿瘤小鼠的机体免疫力达到抗肿瘤的作用。

Objective To investigate the dose-effect relationship of different doses of total saponins of Marsdenia tenacissima (MTTS) combined with doxorubicin (DOX) on anti-tumor activity in H22 hepatoma-bearing mice. Methods H22 hepatoma-bearing mice models were established and randomly divided into model group, DOX (1.5 mg·kg^-1) group, DOX (1.5 mg·kg^-1, once every other day) + MTTS (31.25, 62.50, 125.00, 250.00, 500.00 mg·kg^-1) groups, with 10 mice in each group, and a control group of 10 mice. The DOX administration groups were given the drug on the day after tumor inoculation, once every other day; the DOX + MTTS groups were given DOX and MTTS alternately, one drug per day, by intraperitoneal injection. The control group and the model group were given the same volume of 0.9% sodium chloride solution in the same way. The treatment lasted for 14 d. General behavior, body weight, tumor volume and tumor growth curves were observed. After killing the mice, the tumor tissues were weighed and the tumor inhibition rate was calculated. The spleen and thymus were weighed and the spleen and thymus coefficients were calculat ed.Flow cytometry was used to detect the proportions of T, B and NK cells in the peripheral blood of tumor-bearing mice. Enzymelinked immunosorbent assay was used to detect the levels of serum inflammatory factors. Results The model group had the poorest growth state, with dry and dull hair, poor mental state, reduced activity and decreased food intake. Except for the DOX + MTTS (500.00 mg·kg^-1) group, the combined administration groups showed improved conditions as the dose of MTTS increased, with good activity and mental state. The DOX + MTTS 500 mg·kg^-1 group had dry hair, smaller body weight and volume than the other administration groups, a weak appearance, poor food intake, and began to die from the 7th d. The tumor volume in the model group increased rapidly. Compared with the model group, the tumor growth in the DOX group and the combined administration groups was significantly inhibited. The tumor inhibition rates were 69.68% in the DOX group and 71.43%, 75.95%, 79.15%, 83.38% and 87.90% in the 31.25, 62.50, 125.00, 250.00 and 500.00 mg·kg^-1 combined administration groups, respectively. Compared with the DOX group, MTTS combined with DOX significantly increased the spleen and thymus indices, the percentage of CD4⁺ T lymphocyte subsets, and the CD4⁺/CD8⁺ ratio; significantly increased the percentage of CD19⁺CD20⁺ B cell subsets and CD3^-CD16⁺ NK cell subsets; And significantly decreased the levels of serum inflammatory factors IL-6, IL-8 and TNF-α in tumor-bearing mice. Conclusion The combination of 250.00 mg·kg^-1 MTTS and DOX had the best therapeutic effect and was more effective in reducing the inflammatory level in H22 tumor-bearing mice. MTTS combined with DOX can inhibit tumor growth and achieve anti-tumor effects by enhancing the immunity of H22 tumor-bearing mice.

R285.5

国家中医药管理局高水平中医药重点学科建设项目（zyyzdxk-2023023）；山西省卫生健康委员会重点实验室建设计划项目；山西省中医药管理局科研课题计划项目（2022ZYYC015）