银杏黄酮苷元对多柔比星治疗肝癌的增效减毒作用-中国药房

银杏黄酮苷元对多柔比星治疗肝癌的增效减毒作用

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篇名：	银杏黄酮苷元对多柔比星治疗肝癌的增效减毒作用
TITLE：	Effects of increasing efficacy and decreasing toxicity of ginkgo flavone aglycone on doxorubicin in the treatment of liver cancer
摘要：	目的研究银杏黄酮苷元（GA）对多柔比星（DOX）治疗肝癌的增效减毒作用。方法于ICR小鼠右腋皮下单次接种肝癌细胞H22以建立荷瘤模型，并将造模成功的小鼠随机分为模型对照组、DOX组（2.5mg/kg，隔天尾静脉注射1次）、GA组（30mg/kg，每天灌胃1次）和GA+DOX组（给药方法同单药组），每组6只。药物干预周期为15d。观察各组小鼠的一般生长情况，称定其体质量、瘤体质量并计算抑瘤率，采用金氏公式评估联合用药的效果（Q）。检测各组小鼠血清中甲胎蛋白（AFP）水平，肿瘤组织的病理改变、细胞凋亡情况和血小板-内皮细胞黏附分子1（CD31）的表达水平，以及心脏指数、血清B型钠尿肽（BNP）和N末端脑钠肽前体（NT-proBNP）水平、心脏病理改变和心肌纤维化情况。结果DOX组、GA组、GA+DOX组小鼠的体质量变化百分比（GA组除外）、瘤体质量均较模型对照组显著降低（P＜0.05或P＜0.01），且GA+DOX组的瘤体质量显著低于DOX组（P＜0.01）；3个药物组的抑瘤率分别为54.29％、42.50％、89.29％，两药联合的Q为1.21。各药物组小鼠肿瘤组织均有不同程度坏死，血清AFP水平和肿瘤组织中CD31的表达水平均较模型对照组显著降低（P＜0.05或P＜0.01），肿瘤组织坏死面积百分比和细胞凋亡阳性率（单药组除外）均显著增高（P＜0.05或P＜0.01），且GA+DOX组的细胞凋亡阳性率显著高于DOX组（P＜0.05）。DOX组小鼠的心脏指数显著低于模型对照组（P＜0.05），DOX组、GA+DOX组小鼠的血清BNP、NT-proBNP水平均显著高于模型对照组（P＜0.05或P＜0.01），GA+DOX组小鼠的心脏病理改变和心肌纤维化程度均较DOX组轻微。结论GA和DOX联用具有协同抑瘤作用；GA可增加DOX的促细胞凋亡作用，并有助于降低后者的心脏毒性。
ABSTRACT：	OBJECTIVE To study the effects of increasing efficacy and decreasing toxicity of ginkgo flavone aglycone （GA） on doxorubicin （DOX）in the treatment of liver cancer. METHODS A tumor bearing model was established by inoculating liver cancer cell H 22 into the right axillary skin of ICR mice. The successfully modeled mice were randomly divided into model control group，DOX group （2.5 mg/kg，once every other day ，via tail vein ），GA group （30 mg/kg，once a day ，gavage）and GA+DOX group（the usage was the same as single drug groups ），with 6 mice in each group. The administration cycle was 15 days. The general growth of mice in each group were observed ，body weight and tumor weight were measured ，and the inhibition rate of tumor was calculated. Jin’s formula was used to evaluate the effect of combined medication （Q）. The serum level of alpha-fetal protein（AFP），the pathological changes of tumor tissue ，cell apoptosis and the expression of platelet-endothelial cell adhesion molecule-1（CD31）were detected in each group. The cardiac index，serum levels of B-type natriuretic peptide （BNP）and N-terminal pro-brain natriuretic peptide （NT-pro BNP ），pathological changes of heart and myocardial fibrosis degree were also detected. RESULTS The percentage of body weight change （except for GA group ） and tumor weights of DOX group，GA group and GA + DOX group were all decreased significantly，compared with model control group （P＜0.05 or P＜0.01），while tumor weight of GA+DOX gro up was significantly lower than DOX group （P＜0.01）. Inhibitory rates of tumor in 3 administration groups were 54.29％，42.50％ and 89.29％ respectively，and Q of two-drug combination was 1.21. The tumor tissues of mice in each administration group were necrotic to varying degrees ；the serum level of AFP and the expression of CD31 in tumor tissue were decreased significantly ，compared with model control group （P＜0.05 or P＜0.01）；the percentage of necrosis area of tumor tissue and the positive rate of apoptosis （except for single drug groups ）were significantly increased （P＜0.05 or P＜0.01），while positive rate of apoptosis in GA+DOX group was significantly higher than DOX group （P＜0.05）. Cardiac index of mice in DOX group was significantly lower than model control group （P＜0.01）；serum levels of BNP and NT-pro BNP in DOX group and GA+ DOX group were significantly higher than model control group （P＜0.05 or P＜0.01）；pathological changes of heart and the degree of myocardial fibrosis in GA+DOX group were lower than DOX group. CONCLUSIONS GA combined with DOX show synergistic antitumor effect. GA can strengthen the apoptosis promoting effect of DOX ，and can help to reduce the cardiotoxicity of DOX.
期刊：	2022年第33卷第16期
作者：	宋忠军，朱晓青，何艳，李勇军，陆苑
AUTHORS：	SONG Zhongjun ，ZHU Xiaoqing ，HE Yan，LI Yongjun ，LU Yuan
关键字：	银杏黄酮苷元；多柔比星；增效减毒；肝癌；H22荷瘤小鼠
KEYWORDS：	ginkgo flavone aglycone ；doxorubicin；efficacy enhancing and toxicity reducing ；liver cancer ；H22 tumor-bearing mice
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