百多宁乳剂抗肿瘤药效学研究

【作者】 王佳平；

【导师】 吴英良；

【作者基本信息】 沈阳药科大学 ， 药理学， 2007， 硕士

【摘要】 利用S₁₈₀实体、腹水瘤体内模型进行处方筛选，得出以鸦胆子油和薏苡仁油组方的具有良好抗肿瘤活性的复方乳剂，命名为百多宁乳剂（BDN）；并进一步通过S₁₈₀实体瘤、艾氏腹水癌（EAC）和Lewis肺癌动物模型来考察BDN的临床前抗肿瘤作用及其对氟尿嘧啶（5-Fu）、环磷酰胺（CTX）的增效减毒作用，同时以脾指数、胸腺指数、炭粒廓清能力以及T、B淋巴细胞增殖（MTT法检测）作为免疫学指标考察其对荷S₁₈₀实体瘤小鼠免疫功能的影响，从而对其抗肿瘤作用机制进行初步研究。实验结果表明：（1）复方乳剂中鸦胆子油与薏苡仁油的配比为3∶1时对动物毒性较小，而且抑瘤率和生命延长率最高。所以，确定鸦胆子油与薏苡仁油的最佳配比为3∶1；（2）静脉给予BDN 1g／kg、2g／kg对小鼠S₁₈₀肉瘤的抑瘤效果显著（抑瘤率均＞30％），且优于相同剂量下的康莱特和鸦胆子油乳注射液；静脉给予BDN 2g／kg对荷EAC小鼠的生命延长率均＞50％，虽然低于相同剂量下康莱特，但高于鸦胆子油乳注射液；腹腔注射给予BDN 1g／kg、2g／kg对小鼠Lewis肺癌的抑瘤率均＞30％，且优于相同剂量下的康莱特和鸦胆子油乳注射液；静脉给药的效果优于经口给药；（3）BDN可降低CTX和5-Fu对正常小鼠的毒性；与CTX合用可明显增强其抑瘤作用；（4）BDN能够显著提高荷S₁₈₀肉瘤小鼠的脾指数、炭粒廓清指数K、吞噬系数α及ConA和LPS诱导的T、B淋巴细胞增殖，而对于其胸腺指数则没有影响。更多还原

【Abstract】 In order to sift out the best proportion of brucea javanica oil and semen cocis oil, S₁₈₀ stereo-tumor and ascites tumor-bearing mice were used as experiment objects in the study. And the best prescription, which has potential anticancer activity is named Baiduoning emulsion（BDN）. Then using S₁₈₀ stereo-tumor-bearing mice, EAC-bearing mice and Lewis-bearing mice to observe BDN’s anti-tumor effect and if it can increase Cytoxan（CTX）’s anti-tumor effect, reduce CTX’s and Fluorouracil（5-Fu）’s toxicity in normal mice. In addition index of spleen, index of thymus gland, the phagocytic activities of the peritoneal macrophages, T and B lymphocyte proliferation test（evaluated by MTT assay）were performed to observe BDN’s effects on the S₁₈₀-bearing mice, For the sake of indicating it’s anti-tumor mechanisms.Results of experiments show that, First, the best proportion of brucea javanica oil and semen cocis oil is 3:1. Second, BDN 1 and 2 g·kg^-1 i.v. markedly exerted significant inhibition on S₁₈₀ stereo-tumor, and it had better effect on tumor growth inhibition than brucea javanica oil and semen cocis oil at the same dosages; While in the survival time experiment, BDN could prolong obviously the survival time of mice treated with EAC, though the effect was lower than semen cocis oil, it was higher than brucea javanica oil. BDN 1 and 2 g·kg^-1 i.g. markedly exerted significant inhibition on Lewis, and it had better effect on tumor growth inhibition than brucea javanica oil and semen cocis oil at the same dosages. The therapeutic effect of intravenous injection was better than intragastric administration. Moreover, it could reduce toxicities which were induced by CTX or 5-Fu and strength anti-tumor effect of CTX. Third, BDN could increase the index of spleen, promote the carbon cleared index K and the phagocytic coefficientα, enhanced lymphocyte proliferation significantly in S₁₈₀-bearing mice（alone or with ConA/LPS）. No obvious influence on the index of thymus was observed.更多还原