摘要
目的探讨积雪草酸的抗肿瘤机制。方法制备0.2 mL瘤细胞悬液,分别接种于小鼠左下腹腹腔及右上肢腋部皮下以复制腹水瘤及实体瘤小鼠模型,建模成功后,均随机分为模型组(等体积生理盐水)、5-氟尿嘧啶组(123.3 mg/kg)及积雪草酸高、中、低剂量组(100,75,50 mg/kg)。灌胃生理盐水或相应药物(每10 g体质量0.2 mL),每天1次,连续10 d。记录腹水瘤模型实验中小鼠体质量增长情况,生存时间,计算体质量增长率及生命延长率;记录实体瘤模型实验中小鼠体质量、瘤体质量、脏器质量,计算抑瘤率(IR)、脾脏指数、肝脏指数及胸腺指数;苏木素-伊红染色,观察小鼠瘤体及脾脏组织病理形态,分别采用免疫组织化学法和Western blot法检测小鼠瘤体中热休克蛋白90(Hsp90)、血管内皮生长因子C(VEGF-C)、淋巴管内皮透明质酸受体1(LYVE-1)蛋白表达水平。结果腹水瘤小鼠模型实验中,与模型组比较,各给药组小鼠体质量增长均较缓慢、生存时间均显著延长(P<0.05),积雪草酸高剂量组尤为显著。实体瘤模型小鼠实验中,与模型组比较,5-氟尿嘧啶组和积雪草酸高剂量组小鼠脾脏质量均显著减轻,脾脏指数均显著降低,IR均超过70.00%,瘤体Hsp90,VEGF-C,LYVE-1蛋白表达水平均显著降低(P<0.05);各给药组小鼠瘤体质量均显著减轻(P<0.01);5-氟尿嘧啶组和积雪草酸高剂量组小鼠脾脏髓质结构完整,实体瘤细胞胞核固缩、胞质减少,可见凋亡、坏死的瘤细胞。结论积雪草酸具有一定的抗肿瘤作用,其机制与调控Hsp90、LYVE-1、VEGF-C蛋白表达相关。
Objective To investigate the anti-tumor mechanism of asiatic acid.Methods Tumor cell suspension(0.2 mL)was prepared and subcutaneously inoculated in the left lower abdominal cavity and right upper arm of mice to duplicate ascites tumor and solid tumor mice models.After successful modeling,the mice were randomly divided into the model group(equal volume of normal saline),5-fluorouracil group(123.3 mg/kg)and high-,medium-and low-dose asiatics acid groups(100,75,50 mg/kg),the mice in each group were given normal saline or corresponding drugs(0.2 mL/10 g)by gavage once a day for 10 d.The growth of body mass and survival time of mice in the ascites tumor model experiment were recorded,and the growth rate of body mass and life extension rate were calculated.The body mass,tumor mass and organ mass of mice in the solid tumor model experiment were recorded,and the tumor inhibition rate(IR),and the spleen index,liver index and thymus indexes were calculated.Hematoxylin-eosin staining was used to observe the pathological morphology of tumor body and spleen tissue of mice.The expression levels of heat shock protein 90(Hsp90),vascular endothelial growth factor C(VEGF-C),and lymphatic vessel endothelial hyaluronic acid receptor 1(LYVE-1)protein in the solid tumor were detected by immunohistochemistry and Western blot respectively.Results In the experiment of model mice with ascites tumors,compared with those in the model group,the body mass of mice increased slowly and the survival time of mice was significantly prolonged in each treatment group(P<0.05),especially in the high-dose asiatics acid group.In the experiment of model mice with solid tumors,compared with those in the model group,the spleen mass and spleen index of mice reduced significantly,the IR was more than 70.00%,and the levels of Hsp90,VEGF C,and LYVE-1 protein in the solid tumor reduced significantly in the 5-fluorouracil group and the high-dose asiaticosic acid group(P<0.05),the tumor mass of mice in each treatment group reduced significantly(P<0.01),the struc
作者
陈金元
徐宏
宫丽
苏华
曾宪彪
CHEN Jinyuan;XU Hong;GONG Li;SU Hua;ZENG Xianbiao(Department of Gastrointestinal Surgery,Longhua District People′s Hospital,Shenzhen,Guangdong,China 518110;Department of Pharmacy,Longhua District People′s Hospital,Shenzhen,Guangdong,China 518110;Guangxi Institute of Chinese Medicine&Pharmaceutical Science,Nanning,Guangxi,China 530022)
出处
《中国药业》
CAS
2023年第2期43-47,共5页
China Pharmaceuticals
基金
广东省深圳市龙华区医疗卫生机构区级科研项目[2020059]。
