摘要
[目的]P-糖蛋白(P-gp,编码基因Abcb1)对口服药物生物利用度影响较大,本试验旨在探究黄连素对肉鸡组织Abcb1mRNA表达及对恩诺沙星药动学的影响,为临床合理用药及研究药物间相互作用提供依据。[方法]15只1月龄AA肉鸡随机分为3组:对照组和2个黄连素(40和80 mg·kg^(-1))处理组(n=5)。不同剂量黄连素处理AA肉鸡1 d后采集组织并用荧光定量PCR方法检测组织内Abcb1 mRNA表达的差异;另取15只1月龄AA肉鸡也随机分为对照组和2个黄连素(40和80mg·kg^(-1))处理组,各组鸡处理后口服恩诺沙星10 mg·kg^(-1),并于不同时间点采集血液,用高效液相色谱法测定恩诺沙星的血药浓度,采用3P97软件统计其药代动力学参数。[结果]荧光定量的结果表明:高、低剂量的黄连素处理能显著降低肾脏(P=0.021,P=0.003)、十二指肠(P=0.036,P=0.008)、空肠(P=0.028,P=0.086)和回肠(P=0.026,P=0.003)中Abcb1 mRNA的表达水平,但对肝脏Abcb1 mRNA表达无显著影响。药动学结果表明:恩诺沙星单剂量口服后在肉鸡体内的吸收速率常数(Ka)为(0.96±0.25)h-1,消除半衰期(T1/2ke)为(4.19±0.26)h,达峰时间(Tmax)为(2.66±0.45)h,血浆中峰浓度(Cmax)为(1.83±0.25)μg·m L-1,AUC0~∞和AUC0~2 h分别为(21.78±1.59)和(5.30±0.45)μg·m L-1·h;40和80 mg·kg^(-1)黄连素处理肉鸡后,能显著促进恩诺沙星在肉鸡体内的吸收,减慢其排泄过程,表现为Ka显著升高为(1.66±0.17)和(1.78±0.18)h-1,AUC0~∞和AUC0~2 h显著升高为(28.04±0.54)、(29.80±1.68)μg·m L-1·h和(7.07±0.36)、(7.60±0.58)μg·m L-1·h(P<0.05),Tmax显著下降为(2.13±0.18)、(2.07±0.35 h)(P<0.05)。[结论]不同剂量黄连素引起肉鸡各组织内P-gp编码基因Abcb1的mRNA表达量有所下降,并导致恩诺沙星吸收加快,排泄减慢,药-时曲线下面积增加。该结果可为研究黄连素作为P-gp抑制剂候选药物提供参考。
[Objectives]P-glycoprotein（ P-gp） affects the bioavailability of oral drugs in animals. The aim of the study is to detect the effect of berberine on the mRNA expression and activity of P-gp in broilers,thus providing theoretical support for clinical rational use of drugs and drug-drug interaction. [Methods]In this study,fifteen healthy AA broilers were randomly divided into three groups,control group and two berberine（ 40 and 80 mg·kg^（-1）） treated groups（ n= 5）. The Abcb1 mRNA in different tissues of broilers was detected by real time RT-PCR. The other 15 broilers were treated as above and then orally administrated enrofloxacin at dose of 10 mg·kg^（-1）. Blood samples were collected at different time and then the plasma concentration of enrofloxacin was detected by HPLC method. The pharmacokinetic parameters of enrofloxacin were evaluated from the plasma drug concentrations using software 3P97. [Results]The real time RT-PCR showed that berberine at dose of 80 and 40 mg·kg^（-1）significantly inhibited Abcb1 mRNA in duodenum（ P = 0.036,P = 0.008）,ileum（ P = 0.026,P = 0.003） and kidney（ P = 0.021,P = 0.003）. Berberine significantly inhibited Abcb1 mRNA in jejumn at dose of 80mg·kg^（-1）（ P= 0.028）. The results of HPLC showed that in control group,the parameter Kawas（ 0.96±0.25） h-1,T1 / 2was（ 4.19±0.26） h,Tmaxwas（ 2.66±0.45） h,Cmaxwas（ 1.83±0.25） μg·m L-1,AUC0-∞and AUC0-2 hwere（ 21.78± 1.59） and（ 5.30± 0.45） μg·m L-1·h,respectively. After treating with berberine（ 40 and 80 mg·kg^（-1））,the Ka[（ 1.66±0.17）,（ 1.78±0.18） h-1],T1 / 2ke[（ 5.87±0.48）,（ 7.57±1.46）h],AUC0-∞[（ 28.04±0.54）,（ 29.80±1.68） μg·m L-1·h]and AUC0-2 h[（ 7.07±0.36）,（ 7.60±0.58） μg·m L-1·h]were significantly increased（ P 0. 05）,which indicated that berberine could improve the absorption of enrofloxacin from intestine. [Conclusions]The Abcb1 mRNA expression decreased in different degrees after administrating with
出处
《南京农业大学学报》
CAS
CSCD
北大核心
2016年第3期488-494,共7页
Journal of Nanjing Agricultural University
基金
江苏省高校"青蓝工程"人才项目(2014)
南京农业大学SRT计划项目(1317A25)
