Wistar and Sprague Dawley are the most common strains of rat used in pharmaceutical research and are used interchangeably in pre-clinical drug development. No studies have assessed whether Wistar and Sprague Dawley rats are equivalent in the gastrointestinal factors that influence oral drug absorption, specifically in relation to intestinal transporters. Enzyme-linked immunosorbent assay (ELISA) and liquid chromatography–tandem mass spectrometry (LC-MS/MS) are two reliable methods for quantifying intestinal protein levels with their own distinct advantages and limitations. In this study, P-glycoprotein (P-gp), a key efflux transporter, was quantified using ELISA and LC-MS/MS along the complete intestinal tract of male and female Wistar and Sprague Dawley rats. This work presents that Sprague Dawley rats have innately higher baseline P-gp expression than Wistar rats. Significant sex differences in P-gp expression were identified in the jejunum, ileum and colon between male and female Wistar rats using both techniques, with males exhibiting higher P-gp levels. Sprague Dawley rats showed no sex differences in P-gp expression through ELISA and LC-MS/MS. Both methods demonstrated similar trends for P-gp quantification, but ELISA could offer faster data acquisition. Our findings report significant sex differences between the strains and highlight that Wistar and Sprague Dawley rats are not equivalent in their P-gp expression. As humans exhibit distinct sex differences in intestinal P-gp levels, Wistar rats may therefore be a more suitable pre-clinical animal strain to model oral drug absorption of P-gp substrates in male and female subjects.

中文翻译：

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Wistar 与 Sprague Dawley 大鼠肠道 P-糖蛋白表达的性别差异

Wistar 和 Sprague Dawley 是药物研究中最常见的大鼠品系，在临床前药物开发中可互换使用。没有研究评估 Wistar 和 Sprague Dawley 大鼠在影响口服药物吸收的胃肠道因素方面是否相当，特别是在肠道转运体方面。酶联免疫吸附试验 (ELISA) 和液相色谱-串联质谱 (LC-MS/MS) 是两种可靠的肠道蛋白水平定量方法，具有各自独特的优势和局限性。在这项研究中，使用 ELISA 和 LC-MS/MS 对雄性和雌性 Wistar 和 Sprague Dawley 大鼠的整个肠道进行定量分析，P-糖蛋白 (P-gp)，一种关键的外排转运蛋白。这项工作表明，Sprague Dawley 大鼠的基线 P-gp 表达先天高于 Wistar 大鼠。使用这两种技术在雄性和雌性 Wistar 大鼠的空肠、回肠和结肠中发现了 P-gp 表达的显着性别差异，雄性表现出更高的 P-gp 水平。Sprague Dawley 大鼠通过 ELISA 和 LC-MS/MS 显示 P-gp 表达没有性别差异。两种方法都显示出相似的 P-gp 定量趋势，但 ELISA 可以提供更快的数据采集。我们的研究结果报告了菌株之间的显着性别差异，并强调 Wistar 和 Sprague Dawley 大鼠的 P-gp 表达不相等。由于人类在肠道 P-gp 水平上表现出明显的性别差异，