脂多糖对猪肝脏、肾脏和小肠组织中P-糖蛋白表达的影响  

Effect of LPS on P-glycoprotein localization and expression in live,kidney and small intestines of swine

作　　者：张瑜[1] 郭荔[1] 豆丹丹[1] 任伟龙[1] 王丽平[1] 

机构地区：[1]南京农业大学动物医学院,江苏南京210095

出　　处：《南京农业大学学报》2015年第2期311-317,共7页Journal of Nanjing Agricultural University

基　　金：江苏省青蓝工程项目(2014);江苏高校优势学科建设工程项目(PAPD)

摘　　要：[目的]P-糖蛋白（P-gp）是影响底物药物口服生物利用度至关重要的因素。本试验旨在探究脂多糖（LPS）对猪肝脏、肾脏和小肠组织中P-gp定位和表达的影响,为临床合理有效用药提供理论支持。[方法]采用免疫组织化学SABC法结合DAB显色技术,用抗P-gp的单抗C219对相关组织的P-gp进行定位,进一步采用Image-ProPlus软件对猪肝脏、肾脏、空肠和回肠中P-gp的表达进行半定量分析,检测LPS处理对P-糖蛋白定位和表达的影响。[结果]猪肝脏组织中的P-gp均主要分布于肝细胞间的胆小管细胞膜上,LPS处理3h后P-gp表达量显著上升（P〈0.05）,6h后可降至正常水平。猪肾脏中P-gp主要分布于近端小管和远端小管的细胞膜上,LPS处理6h后P-gp表达量会显著升高（P〈0.05）。猪空肠和回肠中P-gp主要分布于小肠绒毛上皮顶端和小肠腺靠近腔面细胞的顶端,LPS处理3h后在空肠中表达有上升趋势,在6h时表达量会降低至正常水平,但是LPS处理后对猪回肠中P-gp的表达未产生显著影响（P〉0.05）。[结论]LPS处理对猪肝脏、肾脏、空肠和回肠中P-gp的定位无影响,但LPS处理3～6h后可引起P-gp的表达量增加,推测其会对P-gp底物药物在猪体内的药动学过程和临床药效产生一定影响。[Objectives]P-glycoprotein（P-gp） plays a crucial role in the bioavailability of many oral drugs,thus limiting their therapeutic potential.We sought to elucidate the effect of lipopolysaccharide（LPS） on the localization and expression of P-gp in liver,kidney,jejunum and ileum in swine.[Methods]The immunohistochemical SABC method combined with DAB staining method was used to localize the P-gp in tissues of swine with C219 as anti-P-gp monoclonal antibody in this study.Imagepro-plus software was used for semi-quantitative analysis of specific staining of P-gp.[Results]The immunohistochemical results showed that P-gp was distributed in the bile canalicular membrane between hepatocytes in liver of the swine.But compared with those of control group,positive staining of P-gp obviously increased after LPS treatment for 3h（P〈0.05）,and then declined to normal level at 6h.In kidney,the main staining was observed in the membrane of proximal tubule and distal tubule in both healthy and LPS treated pigs,and the expression of P-gp significantly increased after LPS treatment for 6h（P〈0.05）.In jejunum and ileum,the special staining of P-gp was visualized mainly on the apical surface of the small intestine villi and glandular epithelium in both health and LPS treated swine.And the intensity was enhanced following LPS treatment for 3h（P〈0.05） but decreased to normal leval after 6h in the jejunum.No significant difference was found in ileum（P〉0.05）.[Conclusions]The results suggested that the tissues localization of P-gp can not be changed,but the expression level of P-gp could increase following LPS treatment for 3 to 6h,which may have potential role in changing the pharmacokinetics and pharmacodynamic of substrate drugs of P-gp in swine.

关 键 词：LPS 猪 P-糖蛋白 定位 半定量 

分 类 号：S859.7[农业科学—临床兽医学]