基于OCT2、MRP2探讨加味生脉饮对Lewis肺癌小鼠顺铂化疗的增效减毒机制  

Study on the Synergistic and Attenuating Mechanism of Modified Shengmai Decoction on Cisplatin Chemotherapy in Lewis lung Cancer Mice Based on OCT2 and MRP2

作　　者：徐虹云 吴春玉[1] 吴林霖 刘庆南 王丹凝 客蕊[2] XU Hong-Yun;WU Chun-Yu;WU Lin-Lin;LIU Qing-Nan;WANG Dan-Ning;KE Rui(Heilongjiang University of Chinese Medicine,Harbin 150040 Heilongjiang,China;The First Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150040 Heilongjiang,China)

机构地区：[1]黑龙江中医药大学,黑龙江哈尔滨150040 [2]黑龙江中医药大学附属第一医院,黑龙江哈尔滨150040

出　　处：《广州中医药大学学报》2023年第12期3138-3146,共9页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：黑龙江省应用技术研究与开发计划项目(编号:GY2019YF);黑龙江省中医药科研项目(编号:ZHY2020-124)。

摘　　要：【目的】观察加味生脉饮对顺铂化疗Lewis肺癌小鼠有机阳离子转运体2(OCT2)、多药耐药相关蛋白2(MRP2)的影响,探讨其对Lewis肺癌小鼠顺铂化疗的增效减毒机制。【方法】采用腋窝皮下接种Lewis肺癌细胞(LLC)构建肺癌移植瘤小鼠模型,造模成功后随机分为对照组、顺铂组、联合组(顺铂联合加味生脉饮)和生脉饮组,每组7只小鼠,给药14 d。观察4组小鼠一般状态、肿瘤生长情况,肿瘤、肾脏组织病理学以及血清尿素氮(BUN)、肌酐(Cr)浓度。通过免疫组织化学染色(IHC)和Western Blot的方法检测OCT2、MRP2蛋白表达情况,并使用高效液相色谱串联质谱(HPLC-MS/MS)法测定肾脏和肿瘤组织中顺铂含量。【结果】(1)给药结束后,各组小鼠体质量均有下降,顺铂组下降幅度最大,顺铂组体质量变化显著高于联合组、生脉饮组(P<0.05),生脉饮组和联合组小鼠一般状态均优于对照组和顺铂组。(2)干预结束时,顺铂组肿瘤体积和质量小于生脉饮组和对照组,联合组肿瘤体积和质量显著小于顺铂组(P<0.05)。(3)组织病理学结果显示:生脉饮组、对照组肿瘤细胞结构清晰,细胞形态正常;顺铂组与联合组可见肿瘤细胞坏死,肿瘤细胞边缘模糊,联合组肿瘤细胞坏死面积更大。生脉饮组、对照组肾脏细胞形态正常;联合组肾脏细胞损伤较轻,无明显病变;顺铂组肾组织明显病变,肾小管上皮细胞边缘模糊。(4)顺铂组小鼠血清BUN、Cr水平显著高于其他3组(P<0.05)。(5)顺铂组肾脏组织OCT2表达相比对照组显著增加,联合组OCT2表达相比顺铂组显著降低(均P<0.05);顺铂组肿瘤组织MRP2表达相比对照组显著增加,联合组MRP2表达相比顺铂组显著降低(均P<0.05)。(6)联合组肿瘤组织中顺铂含量显著高于顺铂组,联合组肾脏组织中顺铂含量显著低于顺铂组(均P<0.05)。【结论】OCT2、MRP2在顺铂肾脏毒性与耐药性中起重要的调控作用,加味生�Objective To observe the effects of Modified Shengmai Decoction on organic cation transporter 2(OCT2)and multidrug resistance-associated protein 2(MRP2)in Lewis lung cancer mice treated with cisplatin chemotherapy,and to explore the mechanism of its potentiation and toxicity reduction on cisplatin chemotherapy in Lewis lung cancer mice.Methods Axillary subcutaneous inoculation of Lewis lung cancer(LLC)cells were used to construct a mouse model of lung cancer transplantation,and after successful modeling,the mice were randomly divided into the control group,the cisplatin group,the combined group(cisplatin combined with Modified Shengmai Decoction)and the Modified Shengmai Decoction group,with 7 mice in each group,and were administered with the drug for 14 days.The general state,tumour growth,tumour and kidney pathology,and the concentrations of serum urea nitrogen(BUN)and creatinine(Cr)of the 4 groups of mice were investigated.The protein expressions of OCT2 and MRP2 were examined by immunohistochemical staining(IHC)and Western Blot,and the cisplatin content in kidney and tumor tissues was determined using liquid-liquid chromatography.Results(1)The body mass of mice in all groups decreased at the end of drug administration,and the decrease was the largest in the cisplatin group,and the change of body mass in the cisplatin group was significantly higher than that in the combination group and the Modified Shengmai Decoction group(P<0.05),and the general state of mice in the Modified Shengmai Decoction group and the combination group was superior to that in the control group and the cisplatin group.(2)At the end of the intervention,the tumor volume and mass of the cisplatin group were smaller than those of the Modified Shengmai Decoction group and the control group,and the tumor volume and mass of the combination group were significantly smaller than those of the cisplatin group(P<0.05).(3)Histopathological results showed that:the tumor cell structure was clear and the cell morphology was normal in the Modified Sheng

关 键 词：加味生脉饮 顺铂 化疗 肺癌 有机阳离子转运体2(OCT2) 多药耐药相关蛋白2(MRP2) 肾毒性 小鼠 

分 类 号：R285.5[医药卫生—中药学]