山银花提取物对肉鸡口服氟苯尼考药代动力学及代谢转运相关基因表达的影响

Effects of Lonicerae Flos extracts on pharmacokinetics of florfenicol and mRNA expression of metabolic and transport-related genes in broilers

为研究山银花提取物对鸡口服氟苯尼考药代动力学的影响及其作用机制,将30只健康肉公鸡随机平均分成对照组与山银花组,其中山银花组连续7 d灌服山银花提取物(0.20 g/kg,1次/d),对照组则给予相同体积的生理盐水,第8天时选取各组10只鸡按30 mg/kg灌服氟苯尼考,给药后按时间点连续采样,高效液相色谱法(HPLC)检测氟苯尼考血药浓度;2组另5只则按荧光定量RT-PCR方法检测肝脏和空肠中细胞色素P4503A37(CYP3A37)、葡萄糖醛酸转移酶1E(UGT1E)、多药耐药基因1(MDR1)和鸡外源性核受体(CXR)mRNA表达。结果显示:山银花组药-时曲线下面积(AUC_(0~24 h))和平均滞留时间(MRT_(0~24 h))显著增加(P<0.05),表观清除率(CLz)显著降低(P<0.05);与对照组相比,山银花组肝脏和空肠中CYP3A37、UGT1E、CXR mRNA表达显著降低(P<0.05),肝脏、空肠MDR1 mRNA表达无显著差异(P>0.05)。结果表明:联用山银花后,氟苯尼考在鸡体内药代动力学参数(AUC、MRT和CLz)发生显著变化,可能与山银花抑制CYP3A37、UGT1E、CXR mRNA在肝脏和空肠的表达有关。

Lonicerae Flos,called Shanyinhua(SYH)in Chinese,is commonly used to treat bacterial diseases in combination with other antibiotics,such as florfenicol,one of the most widely used veterinary antibiotics in animal husbandry.However,the effects of SYH on the pharmacokinetics of florfenicol are not known.Thus,we studied the effects of SYH on florfenicol pharmacokinetics and the mRNA expression of drug-metabolizing enzymes/efflux transporters in broilers.Experimental broilers were given SYH extract(0.2 g/kg)or 0.9%sodium chloride solution by intragastric administration for 7 days.They were then fed with florfenicol by intragastric administration(30 mg/kg BW)on the eighth day.Then,blood samples were collected continually from the broilers at at time points,and the plasma concentrations of florfenicol were estimated with ultra-high-performance liquid chromatography.The mRNA expression levels of cytochrome P4503 A37(CYP3 A37),UDP-glucuronosyltransferase 1E(UGT1E)and multi-drug resistance 1(MDR1)in the liver and jejunum were analyzed with real-time polymerase chain reaction.The results were that AUC_(0-24 h) and MRT_(0-24 h) of florfenicol were significantly increased and the CLz/F was significantly decreased by SYH.The mRNA expression levels of CXR,CYP3 A37 and UGT1 E were down-regulated.To susm up,SYH increased the bioavailability and residence time of florfenicol,probably by decreasing the mRNA expression levels of CXR,CYP3 A37 and UGT1 E in the liver and jejunum of broilers.