本文選題：黃連素　切入點：P-gp　出處：《南京農業(yè)大學學報》2016年03期 　論文類型：期刊論文

【摘要】：[目的]P-糖蛋白(P-gp,編碼基因Abcb1)對口服藥物生物利用度影響較大,本試驗旨在探究黃連素對肉雞組織Abcb1mRNA表達及對恩諾沙星藥動學的影響,為臨床合理用藥及研究藥物間相互作用提供依據。[方法]15只1月齡AA肉雞隨機分為3組:對照組和2個黃連素(40和80 mg·kg~(-1))處理組(n=5)。不同劑量黃連素處理AA肉雞1 d后采集組織并用熒光定量PCR方法檢測組織內Abcb1 mRNA表達的差異;另取15只1月齡AA肉雞也隨機分為對照組和2個黃連素(40和80mg·kg~(-1))處理組,各組雞處理后口服恩諾沙星10 mg·kg~(-1),并于不同時間點采集血液,用高效液相色譜法測定恩諾沙星的血藥濃度,采用3P97軟件統(tǒng)計其藥代動力學參數(shù)。[結果]熒光定量的結果表明:高、低劑量的黃連素處理能顯著降低腎臟(P=0.021,P=0.003)、十二指腸(P=0.036,P=0.008)、空腸(P=0.028,P=0.086)和回腸(P=0.026,P=0.003)中Abcb1 mRNA的表達水平,但對肝臟Abcb1 mRNA表達無顯著影響。藥動學結果表明:恩諾沙星單劑量口服后在肉雞體內的吸收速率常數(shù)(Ka)為(0.96±0.25)h-1,消除半衰期(T1/2ke)為(4.19±0.26)h,達峰時間(Tmax)為(2.66±0.45)h,血漿中峰濃度(Cmax)為(1.83±0.25)μg·m L-1,AUC0~∞和AUC0~2 h分別為(21.78±1.59)和(5.30±0.45)μg·m L-1·h;40和80 mg·kg~(-1)黃連素處理肉雞后,能顯著促進恩諾沙星在肉雞體內的吸收,減慢其排泄過程,表現(xiàn)為Ka顯著升高為(1.66±0.17)和(1.78±0.18)h-1,AUC0~∞和AUC0~2 h顯著升高為(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顯著下降為(2.13±0.18)、(2.07±0.35 h)(P0.05)。[結論]不同劑量黃連素引起肉雞各組織內P-gp編碼基因Abcb1的mRNA表達量有所下降,并導致恩諾沙星吸收加快,排泄減慢,藥-時曲線下面積增加。該結果可為研究黃連素作為P-gp抑制劑候選藥物提供參考。
[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 鹵0.25h-1, the elimination half-life T1 / 2kewas 4.19 鹵0.26h, the peak time Tmaxwas 2.66 鹵0.45h. and the plasma peak concentration (Cmax) was 2.66 鹵0.45h. the results of pharmacokinetics showed that the absorption rate constant of enrofloxacin in broilers was 0.96 鹵0.25h-1, the elimination half-life was 4.19 鹵0.26h, the peak time Tmaxwas 2.66 鹵0.45h. 1. 83 鹵0. 25) 渭 g 路ml -1 AUC0 ~ 鈭，

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