[关键词]
[摘要]
目的 考察青蒿鳖甲方对肿瘤炎症反应的干预作用,分析其干预作用的量效关系以及君药青蒿及青蒿鳖甲组合在全方中的作用。方法 S180荷瘤小鼠随机分为青蒿组(1.5 g/kg),青蒿鳖甲组合组(1.5 g/kg),青蒿鳖甲方低、中、高剂量(0.75、1.5、3.0 g/kg)组及模型组,每天ig给药1次,连续给药10 d。停药后称各组小鼠肿瘤质量,免疫组织化学法与Western blotting法检测肿瘤组织中环氧合酶-2(COX-2)、血管内皮生长因子(VEGF)蛋白表达,HE染色、光学显微镜计数白细胞,ELISA法测定荷瘤小鼠血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、前列腺素E2(PGE2)水平。结果 青蒿鳖甲组合较单一青蒿有更强的抑瘤作用和较强的PGE2抑制作用;青蒿鳖甲方明显升高细胞因子TNF-α、IL-1β水平,明显抑制COX-2、VEGF蛋白表达和肿瘤生长;青蒿鳖甲方低、中、高剂量抑制肿瘤生长的作用无明显量效关系。结论 青蒿鳖甲方通过对TNF-α和IL-1β的调控作用干预肿瘤炎症反应,进而产生抑制肿瘤生长作用。
[Key word]
[Abstract]
Objective To observe the intervention of antitumor inflammatory response of Qinghao-Biejia Formula, to analyze the dose-effect relationship of the intervention, and to investigate the roles of Qinghao and Qinghao-Biejia combination in the formula. Methods The ICR mice bearing S180 sarcoma were randomly divided into six groups: Qinghao (1.5 g/kg), Qinghao-Biejia combination (1.5 g/kg), Qinghao-Biejia Formula (0.75, 1.5, and 3.0 g/kg), and model groups. The drugs were ig administered once daily for 10 d continuously. After the last administration, the tumor weights in mice of each group were detected. The expression of COX-2 and VEGF protein in S180 sarcoma was detected by immunohistochemistry and Western blotting methods; Leukocyte numbers were counted by HE staining and optical microscope. Levels of TNF-α, IL-1β, and PGE2 in mice serum were measured by ELISA assay. Results Qinghao-Biejia combination had much stronger antitumor effects and inhibition on PGE2 than single Qinghao. Qinghao-Biejia Formula improved the levels of TNF-α and IL-1β significantly, and also decreased the expression of COX-2 and VEGF protein obviously. No obvious dose-effect relationship was observed in the inhibition on tumor growth by low-, mid-, and high-dose of Qinghao-Biejia Formula. Conclusion Qinghao-Biejia Formula has the inhibition on tumor and interferes the inflammatory response through the regulation of TNF-α and IL-1β.
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[基金项目]
浙江省自然科学基金资助项目(Y207432)