目的 研究不同劑量的通關(guān)藤總皂苷（MTTS）聯(lián)合阿霉素（DOX）對H22肝癌小鼠抗腫瘤的量效關(guān)系。方法 建立H22肝癌小鼠模型，隨機分為模型組、DOX（1.5 mg·kg^-1）組、DOX（1.5 mg·kg^-1，隔天給藥1次） ＋MTTS（分別設(shè)31.25、62.50、125.00、250.00、500.00 mg·kg^-1）組，每組10只，另設(shè)對照組10只。DOX給藥組在腫瘤接種后次日給藥，每隔1天給藥1次； DOX＋ MTTS組DOX、MTTS輪流給藥，每天給1種藥，ip給藥；對照組和模型組同法給予相同體積的0.9%氯化鈉溶液，連續(xù)給藥14 d。對小鼠進行一般行為觀察、體質(zhì)量觀察、測量腫瘤體積并繪制腫瘤生長曲線；殺鼠后，取瘤組織稱質(zhì)量，并計算抑瘤率；取脾臟、胸腺稱質(zhì)量，并計算脾臟系數(shù)、胸腺系數(shù)；利用流式細胞術(shù)檢測荷瘤小鼠外周血中T、B淋巴細胞、自然殺傷（NK）細胞比例；采用酶聯(lián)免疫法檢測血清炎癥因子水平。結(jié)果 模型組小鼠生長狀態(tài)最差，且毛發(fā)枯槁，沒有光澤，精神狀態(tài)不佳，活動減少，飲食減少；除DOX＋MTTS（500.00 mg·kg^-1）組外，聯(lián)合給藥組隨著MTTS劑量增大，狀態(tài)逐步變好，活動以及精神狀態(tài)良好； DOX＋MTTS 500 mg·kg^-1組小鼠毛發(fā)枯槁，體質(zhì)量與體積較其余各給藥組都偏小，形態(tài)瘦弱，飲食不佳，從第7天開始出現(xiàn)死亡。模型組腫瘤體積快速增長，與模型組相比，DOX組和聯(lián)合給藥組腫瘤生長均出現(xiàn)明顯抑制； DOX組抑瘤率69.68%，31.25、62.50、125.00、250.00、500.00 mg·kg^-1聯(lián)合用藥組抑瘤率分別為71.43%、75.95%、79.15%、83.38%、87.90%。與DOX組相比，MTTS協(xié)同DOX能夠顯著升高腫瘤小鼠脾臟指數(shù)、胸腺指數(shù)，顯著增加CD4⁺T淋巴細胞亞群百分率，減少CD8⁺T淋巴細胞亞群百分率，升高CD4⁺/CD8⁺；顯著升高CD19⁺CD20⁺B細胞亞群百分率、CD3^-CD16⁺NK細胞亞群的百分率；顯著降低荷瘤小鼠血清炎癥因子白細胞介素（IL）-6、IL-8、腫瘤壞死因子-α（TNF-α）水平。結(jié)論 250.00 mg·kg^-1 MTTS聯(lián)合阿霉素的治療效果最佳，降低H22荷瘤小鼠體內(nèi)炎癥因子水平更為突出。MTTS協(xié)同DOX能夠抑制腫瘤生長，通過提高H22腫瘤小鼠的機體免疫力達到抗腫瘤的作用。

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

國家中醫(yī)藥管理局高水平中醫(yī)藥重點學科建設(shè)項目（zyyzdxk-2023023）；山西省衛(wèi)生健康委員會重點實驗室建設(shè)計劃項目；山西省中醫(yī)藥管理局科研課題計劃項目（2022ZYYC015）