长期COVID中损伤:对实验小鼠的研究
Rajalakshmi Ramamoorthy1, Hussain Hussain2, Natalia Ravelo1
1Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Biology
|August 26, 2023
概括
长期的COVID可能会导致脏持续受损. 这项小鼠研究表明,纤维化事件可能在感染早期开始,可能导致纤维化. 治疗向可以预防长期的COVID脏并发症.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
背景情况:
- SARS-CoV-2 感染 (PASC) 或长期COVID的急性后续症状通常涉及多个器官系统.
- 损伤是COVID-19患者的一种已知的并发症,得到动物模型的研究结果的支持.
- 之前的研究报告了小鼠肝炎病毒-1 (MHV-1) 的急性和长期感染后小鼠脏的病理生理变化.
研究的目的:
- 在长期冠状病毒感染的小鼠模型中研究病理的分子机制.
- 确定与感染后纤维化相关的特定信号通路和生物标志物.
- 评估针对病毒尖端蛋白相互作用的治疗潜力.
主要方法:
- 在急性 (7天) 和长期 (12个月) 的MHV-1感染后对小鼠脏的病理检查.
- 关键纤维和炎症标志物的定量mRNA分析.
- 免疫血栓检测以评估蛋白质水平的变化.
- 在体内用一种合成 (SPIKENET) 抑制尖蛋白结合的治疗.
主要成果:
- 长期的MHV-1感染导致膜胀,炎症,管状缩和免疫细胞透.
- 在长期感染中观察到TGF-β1,FGF23,NGAL,IL-18,HIF1-α,TLR2,YKL-40和B2M的mRNA水平升高;在急性感染中,NGAL升高.
- 蛋白质分析显示长期感染时HIF1-α,TLR-2和EGFR的增加,而急性感染时KIM-1和MMP-7的增加.
- 在急性感染中,SPIKENET治疗降低了NGAL mRNA,在长期感染中降低了TGF-β1,BCL3 mRNA,EGFR,HIF1-α和TLR-2蛋白水平.
结论:
- 纤维化可能在冠状病毒感染的早期开始,导致长期COVID相关的并发症.
- 特定的分子标记物如NGAL,TGF-β1和HIF1-α都与纤维化发展有关.
- 针对像SPIKENET这样的药物与病毒尖端蛋白相互作用,有望缓解急性和长期损伤.
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