LPS对肉鸡空肠多药耐药相关蛋白2(MRP2)mRNA表达及其底物酮康唑小肠渗透性的影响

Effect of lipopolysaccharide on MRP2 mRNA expression and transport function of the substrate ketoconazole in the small intestine of broilers

为了探讨脂多糖对肉鸡空肠中多药耐药相关蛋白2(MRP2)mRNA表达及转运功能的影响,采用荧光定量PCR方法检测脂多糖处理6 h和12 h后对健康肉鸡空肠组织中MRP2 mRNA表达的影响;采用小肠原位单向灌流试验测定了不同剂量脂多糖(5 mg/kg和15 mg/kg)对酮康唑空肠渗透性的影响。结果显示:经LPS处理6和12 h后,空肠中MRP2 mRNA的表达水平均极显著降低(P<0.01);鸡小肠原位单向灌流试验显示高浓度的脂多糖(15 mg/kg)能显著增加酮康唑在小肠的有效渗透率(Peff)(P<0.05)。试验表明,脂多糖能抑制肉鸡空肠组织中MRP2 mRNA的表达并对空肠的外排转运功能产生影响,从而促进其底物药物的小肠渗透性,进而可能会影响其体内生物利用度。该结果可为炎症状态下肉鸡的合理用药提供理论支持。

This study was to investigate the effect of lipopolysaccharide on mRNA expression and transport function of multidrug resistance-related protein 2(MRP2)in broilers.Sampled broilers were treated by lipopolysaccharide for 6 and 12 h,respectively;and the mRNA expression of MRP2 was detected by real-time PCR,and the permeability of ketoconazole in the small intestine of the birds was determined by chicken in situ single-pass intestinal perfusions after treated with different doses of lipopolysaccharide(5 mg/kg and 15 mg/kg).The results showed that,the expression levels of MRP2 mRNA in the jejunum were all significantly decreased by LPS treated for 6 and 12 h,respectively(P<0.01).The results of chicken small intestine in situ perfusion showed that high concentrations of lipopolysaccharide(15 mg/kg)significantly increased the effective permeability(Peff)of ketoconazole in the small intestine(P<0.05).This indicated that lipopolysaccharide inhibited the expression of MRP2 mRNA in chickens and had an effect on the efflux transport function of the small intestine,thus increasing the bioavailability of MRP2 substrates.The present study provided theoretical support for the rational use of drugs for broilers under inflammatory status.