不同剂量黄连素对肉鸡组织P-gp编码基因Abcb1 mRNA表达及口服恩诺沙星药动学的影响

发布时间：2018-03-11 10:51

  本文选题：黄连素　切入点：P-gp　出处：《南京农业大学学报》2016年03期 　论文类型：期刊论文

【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(P0.05),Tmax显著下降为(2.13±0.18)、(2.07±0.35 h)(P0.05)。[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。
[Abstract]:[objective] P-gp1 (encoding gene Abcb1) has great effect on the bioavailability of oral drugs. The purpose of this study was to investigate the effects of berberine on the expression of Abcb1mRNA in broiler tissues and on the pharmacokinetics of enrofloxacin. [methods] Fifteen one-month-old AA broilers were randomly divided into three groups: control group and two groups treated with berberine 40 and 80 mg 路kg ~ (-1)). Different doses of berberine treated AA broilers for 1 day. The difference of Abcb1 mRNA expression in tissues was detected by fluorescence quantitative PCR. Another 15 one-month-old AA broilers were randomly divided into two groups: control group and two groups treated with berberine 40 and 80 mg 路kg ~ (-1). Each group was treated with enrofloxacin (10 mg 路kg ~ (-1)). Blood samples were collected at different time points, and the blood concentration of enrofloxacin was determined by high performance liquid chromatography (HPLC). The pharmacokinetic parameters were calculated by 3P97 software. [results] the results of fluorescence quantitative analysis showed that high and low doses of berberine could significantly reduce the expression of Abcb1 mRNA in the kidney, duodenum, duodenum, jejunum, jejunum, and ileum, respectively. The results of pharmacokinetics showed that the absorption rate constant of enrofloxacin in broilers was 0.96 卤0.25h-1, the elimination half-life T1 / 2kewas 4.19 卤0.26h, the peak time Tmaxwas 2.66 卤0.45h. and the plasma peak concentration (Cmax) was 2.66 卤0.45h. the results of pharmacokinetics showed that the absorption rate constant of enrofloxacin in broilers was 0.96 卤0.25h-1, the elimination half-life was 4.19 卤0.26h, the peak time Tmaxwas 2.66 卤0.45h. 1. 83 卤0. 25) 渭 g 路ml -1 AUC0 ~ 鈭，

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