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[摘要]
目的 探究氢溴酸槟榔碱对大鼠肝肾转运体表达的影响。方法 通过给雄性Wistar大鼠ig氢溴酸槟榔碱(0.8、4、20 mg/kg)21 d,应用荧光RT-PCR检测肝、肾组织中13种转运体mRNA的表达量,考察氢溴酸槟榔碱对大鼠肝、肾转运体mRNA表达的影响。结果 氢溴酸槟榔碱低剂量时显著抑制了肝脏MRP2和MDR1A mRNA表达,但显著诱导了肾脏MRP5 mRNA表达。氢溴酸槟榔碱高剂量时显著抑制了肝脏OCT2、OAT2、OCTN2、OATP1A1、OATP1A4、OATP2B1、MRP2和MDR1A,以及肾脏MRP2、BCRP、MDR1A的mRNA表达水平,但显著上调了肾脏OCTN2、OATP1A1、OATP1A4及MRP5的mRNA表达量,且对上述转运体mRNA表达的影响有一定剂量依赖性。结论 由于肝肾转运体表达与功能的改变会引起药物相互作用,临床上应给予槟榔嗜好者更多关注,以避免发生不良药物相互作用。
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[Abstract]
Objective To investigate the protective effect of ginseng fruit anthocyanins (GFA) against acetaminophen (AP) induced liver damage in mice and its possible mechanism. Methods The model of AP induced liver injury was established, and the GFA protection for liver damage was observed. Thirty-two male ICR mice were randomly divided into normal group, AP group, GFA with 200 mg/kg dose group, and GFA with 400 mg/kg group. Colorimetric method was used to assay the contents of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), activity of glutathione (GSH) and malondialdehyde (MDA) content of liver homogenate in mice, and observe liver tissue pathological section. Results GFA obviously reduced the level of ALT in serum, inhibited the level of MDA, and enhanced activity of GSH in liver tissue. The H&E and Hoechst 33258 staining results indicated that GFA could obviously improve the degree of liver tissue necrosis and apoptosis, narrow the scope of necrosis, and relieve the inflammatory cell infiltration. By inflammatory factor of iNOS, COX-2 immunohistochemical staining and nitrification stress index of 3-NT immunofluorescence, GFA could inhibit nitration stress and the expression of inflammatory cytokines. Conclusion GFA has certain protective effect on AP-induced acute liver injury and its mechanism may relate to antioxidant effect, inhibition of nitrification stress, alleviation inflammation reaction and inhibiting apoptosis.
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[基金项目]
教育部大学生创新创业训练计划项目(201410512010)