梅花素-黄素组合改善宿主线粒体呼吸,并降低了梅花素在感染Plasmodium berghei的小鼠中的线粒体毒性作用
John Oludele Olanlokun1, Oshireku Wisdom Abiodun1, Adekunle Theophilus Adegbuyi2
1Laboratories for Biomemebrane Research and Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Current research in pharmacology and drug discovery
|May 10, 2024
概括
这项研究研究了等离子杆菌感染和治疗如何影响小鼠的基因表达. 通过调节关键基因,将梅花素与黄素结合使用提高了治疗效果,并降低了毒性.
科学领域:
- 寄生虫学和分子生物学
- 药理学和毒理学 药理学和毒理学
背景情况:
- 疟原虫感染对健康构成重大挑战,对其对宿主基因表达的影响的了解有限.
- 现有的抗疟疾药物有效地杀死寄生虫,但可能对宿主分子通路产生无特征的影响.
- 在感染和治疗期间调查基因表达变化对于理解疟疾病原和药物机制至关重要.
研究的目的:
- 为了确定Plasmodium berghei感染和用梅花素 (MF) 和黄素 (CM) 治疗对宿主基因表达的影响.
- 评估MF和CM单独和组合对与寄生虫感染和宿主反应相关的特定基因的影响.
- 评估这些治疗对糖解,毒性和抗氧化剂标记物的影响.
主要方法:
- 在瑞士小鼠中使用克洛洛昆敏感和耐药菌株诱导Plasmodium berghei感染.
- 治疗小鼠的方法包括蒸水,梅花素,黄素或它们的组合.
- 对FIKK12,AQP3,P38 MAPK,NADH氧降解酶和细胞氧化酶的基因表达分析 (PCR) 在肝脏和红细胞RNA上进行.
- 用ELISA测试来确定糖解,毒性和抗氧化剂的标志物.
主要成果:
- 单独或与黄素调节的FIKK12和AQP3基因表达相结合的梅花素在易感和耐药疟疾模型中.
- 黄素降低了P38 MAPK的表达,而梅花素-黄素治疗恢复了因感染而被抑制的NADH氧化还原酶和细胞氧化酶的表达.
- 治疗抑制了葡萄糖分解和毒性标记物,并改善了抗氧化剂系统,黄素在疗效和毒性预防方面发挥了关键作用.
结论:
- 疟原虫感染和抗疟疾治疗显著调节宿主基因表达.
- 与梅花和黄素的联合治疗显示出增强的治疗效果,并降低宿主毒性.
- 黄素在实现有效治疗结果和减轻疟疾的不良影响方面发挥着至关重要的作用.
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