摘要
目的:钩吻配伍玉叶金花对外排转运蛋白乳腺癌耐药蛋白(BCRP)和细胞色素P450 3A11(CYP3A11)的影响,探讨其配伍减毒的机制;同时添加核受体激活剂干预探讨核受体是否在该过程中有调节作用。方法:将C57BL/6小鼠分为空白组,钩吻组(GE组,0.25 g·kg^(-1)),钩吻配伍玉叶金花组(GE+MP组,0.25 g·kg^(-1)+10 g·kg^(-1)),钩吻+孕烷X受体(PXR)激活剂(利福平)组(GE+Rif组,0.25 g·kg^(-1)+50 mg·kg^(-1)),配伍+利福平组(GE+MP+Rif组,0.25 g·kg^(-1)+10 g·kg^(-1)+50 mg·kg^(-1)),钩吻+组成型雄甾烷受体(CAR)激活剂{1,4-双[2-(3,5-二氯吡啶氧)]苯,TCPOBOP}组(GE+TCP组,0.25 g·kg^(-1)+0.5 mg·kg^(-1)),配伍+CAR激活剂组(GE+MP+TCP组,0.25 g·kg^(-1)+10 g·kg^(-1)+0.5 mg·kg^(-1))。连续给药14 d,末次给药1 h后脱颈处死小鼠,取肝组织。左肝组织采用苏木素-伊红(HE)染色观察其病理学变化;右肝组织采用实时荧光定量聚合酶链式反应(Real-time PCR),蛋白免疫印迹法(Western blot)对其进行mRNA及蛋白水平的检测,检测其对BCRP,CYP3A11基因和蛋白的影响。结果:GE+Rif组小鼠存活率25%,存活率最低,GE组存活率40%,GE+MP组存活率为80%,其他组均存活未见死亡。GE组小鼠肝脏细胞出现明显病变,与GE组比较,GE+MP组肝细胞病理状态都有所缓解;GE+Rif组小鼠肝脏细胞病理状态严重,与GE+Rif组比较,GE+MP+Rif组小鼠肝脏细胞肝细胞病变有所缓解;GE+TCP组小鼠肝脏出现轻微病变,GE+MP+TCP组小鼠肝脏细胞病变不明显;与GE+MP组比较,GE+MP+TCP组病变程度有轻微缓解但差异不大。与空白组比较,GE组BCRP蛋白及mRNA表达明显下调(P<0.05,P<0.01);GE组CYP3A11蛋白表达显著下调(P<0.01),mRNA表达有下调趋势但差异无统计学意义。与GE组比较,GE+MP组BCRP蛋白及mRNA表达均明显上调(P<0.05,P<0.01);CYP3A11蛋白及mRNA表达有上调趋势,但差异无统计学意义。与GE组比较,GE+Rif组BCRP蛋白表达明显下调(P<0.05);与GE+MP组比较,GE+MP+Rif组BCRP蛋�
Objective: To explore the effect of Gelsemium elegans combined with Mussaenda pubescens on efflux transporter breast cancer resistance protein(BCRP) and cytochrome P450 3A11(CYP3A11)and their attenuation mechanism,and to investigate whether the nuclear receptors were involved in such regulation by intervening it with nuclear receptor activators. Method: C57 BL/6 mice were divided into the blank group,G. elegans(GE,0.25 g·kg^(-1))group,GE + M. pubescens(MP)(0.25 g·kg^(-1)+10 g·kg^(-1))group,GE + pregnane X receptor(PXR)activator(rifampicin)(GE + Rif,0.25 g·kg^(-1)+50 mg·kg^(-1))group,GE + MP +Rif(0.25 g·kg^(-1)+10 g·kg^(-1)+50 mg·kg^(-1))group,GE + constitutive androstane receptor(CAR)activator(1,4-Bis[2-(3,5-Dichloropyridyloxy)] benzene,TCPOBOP)(GE + TCP,0.25 g·kg^(-1)+0.5 mg·kg^(-1))group,and GE + MP + TCP(0.25 g·kg^(-1)+10 g·kg^(-1)+0.5 mg·kg^(-1))group. The medication lasted for 14 successive days. One hour after the last administration,the mice were sacrificed by cervical dislocation and the liver tissue was harvested. The left liver tissue was stained with hematoxylin-eosin(HE)for observing the pathological changes.The right liver tissue was used for BCRP and CYP3A11 mRNA and protein expression detection by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)and Western blot. Result: The survival rates of mice in the GE + Rif group,GE group,and GE + MP group were 25%(the lowest),40%,and 80%,respectively,and no death was observed in the other groups. Compared with the obvious lesions in the liver cells of the GE group,the pathological changes in liver cells of the GE + MP group were alleviated,while those in the GE + Rif group were worsened. Compared with the GE + Rif group,the GE + MP + Rif group exhibited relieved pathological changes in liver cells. Both the GE + TCP group and the GE + MP + TCP group showed mild liver lesions. The comparison with the GE + MP group revealed that the pathological changes in the GE + MP + TCP group were slightly relieved. Compared with the
作者
朱翠萍
高汉云
赵茜茜
刘翔翔
黄美霞
王英豪
ZHU Cui-ping;GAO Han-yun;ZHAO Qian-qian;LIU Xiang-xiang;HUANG Mei-xia;WANG Ying-hao(Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2022年第1期58-64,共7页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81773921)
福建省自然科学基金项目(2019J01343)。
