P-糖蛋白表达对 Sprague Dawley 大鼠幽门螺杆菌感染标准治疗的影响。

The influence of P-glycoprotein expression in the standard treatment of Helicobacter pylori infection in Sprague Dawley rats.

机构信息

Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

Quality Use of Medicine Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

出版信息

Daru. 2021 Jun;29(1):13-22. doi: 10.1007/s40199-020-00377-2. Epub 2021 Jan 6.

DOI:10.1007/s40199-020-00377-2

PMID:33405191

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8149563/

Abstract

BACKGROUND

P-glycoprotein (P-gp) is an Adenosine triphosphate (ATP) dependent drug-efflux pump which is located abundantly in the stomach and protects the gut mucosa from xenobiotic.

OBJECTIVE

The purpose of this study was to investigate the influence of P-gp modulation on the efficacy of treatment regimen.

METHOD

P-gp modulation in rats was performed by using P-gp inducer (150 mg/kg rifampicin) and P-gp inhibitor (10 mg/kg cyclosporine A) for 14 days prior to be infected with Helicobacter pylori (H. pylori). The rats were further divided into groups, which were normal control, vehicle control, antibiotics and omeprazole, antibiotics only and omeprazole only for another 2 weeks of treatment. The ulcer formation and P-gp expression were determined by using macroscopic evaluation and western blot analysis, respectively.

RESULTS

The highest P-gp expression was shown in the induced P-gp rats (2.00 ± 0.68) while the lowest P-gp expression was shown in the inhibited P-gp rats (0.45 ± 0.36) compared to the normal P-gp rats. In all groups, the rats which were infected with H. pylori, had a significant increase (p < 0.05) in P-gp expression level and a more severe ulcer formation compared to the healthy rats. The ulcer developed at different levels in the rats with inhibited, induced, or normal P-gp expression. After receiving the standard therapy for H. pylori, it was observed that the healing rate for ulcer was increased to 91% (rats with inhibited P-gp expression), 82% (rats with induced P-gp expression) and 75% in rats with normal P-gp. The use of rifampicin to induce P-gp level was also shown to be effective in eradicating the H. pylori infection.

CONCLUSION

The synergism in the standard therapy by using two antibiotics (clarithromycin and amoxicillin) and proton pump inhibitor (omeprazole) have shown to effectively eradicate the H. pylori infection. Thus, P-gp expression influenced the effectiveness of the treatment.

摘要

背景

P-糖蛋白（P-gp）是一种三磷酸腺苷（ATP）依赖性药物外排泵，在胃中大量存在，可保护肠道黏膜免受外源性物质的侵害。

目的

本研究旨在探讨 P-糖蛋白调节对治疗方案疗效的影响。

方法

在感染幽门螺杆菌（H. pylori）之前，使用 P-糖蛋白诱导剂（利福平 150mg/kg）和 P-糖蛋白抑制剂（环孢素 A 10mg/kg）对大鼠进行 P-糖蛋白调节，持续 14 天。然后，将大鼠进一步分为正常对照组、溶媒对照组、抗生素和奥美拉唑组、抗生素组和奥美拉唑组，再进行 2 周的治疗。通过宏观评估和 Western blot 分析分别测定溃疡形成和 P-糖蛋白表达。

结果

与正常 P-糖蛋白大鼠相比，诱导 P-糖蛋白大鼠的 P-糖蛋白表达最高（2.00±0.68），而抑制 P-糖蛋白大鼠的 P-糖蛋白表达最低（0.45±0.36）。在所有组中，感染 H. pylori 的大鼠 P-糖蛋白表达水平显著升高（p<0.05），且溃疡形成较健康大鼠更为严重。在 P-糖蛋白表达受抑制、诱导或正常的大鼠中，溃疡的发展程度不同。在接受 H. pylori 的标准治疗后，观察到抑制 P-糖蛋白表达的大鼠溃疡愈合率提高至 91%（大鼠），诱导 P-糖蛋白表达的大鼠溃疡愈合率提高至 82%（大鼠），正常 P-糖蛋白大鼠的溃疡愈合率提高至 75%。用利福平诱导 P-糖蛋白水平也显示出有效根除 H. pylori 感染的效果。