基于白细胞介素-6R、蛋白酶活化受体4和嘌呤能受体探讨炎症-凝血正反馈回路在新型冠状病毒诱发急性肺损伤中的作用机制  

Investigating the action mechanism of inflammation-coagulation positive feedback loop on SARS-CoV-2-induced ALI based on IL-6R, PAR4 and P2Y12

作　　者：冯大鹏 张艳 张丽 FENG Dapeng

机构地区：[1]甘肃省中心医院,甘肃兰州730000

出　　处：《中医临床研究》2022年第14期34-37,共4页Clinical Journal Of Chinese Medicine

摘　　要：新型冠状病毒肺炎(简称新冠肺炎)是一场波及全球范围的突发性公共卫生事件。新型冠状病毒(SARS-CoV-2可能通过S蛋白-血管紧张素转化酶2(Angiotensin-converting Enzyme 2,ACE2)途径感染细胞,引起气管上皮细胞损伤及肺泡损伤,进一步引起炎症因子风暴,并最终导致急性肺损伤(Acute Lung Injury,ALI)。已有研究表明,白细胞介素-6(Interleukin-6,IL-6)被认为是新冠肺炎患者肺损伤细胞因子风暴发病的关键因子,炎症亦可引起内皮细胞损伤,导致凝血障碍,并进一步增强炎症因子的释放,形成炎症-凝血的正反馈回路,进一步加重肺损伤。其次,SARS-CoV-2与ACE2的相互作用可导致血管紧张素信号失调、炎症和组织损伤等,并使蛋白酶活化受体4(Protease-activated Receptor 4,PAR4)和嘌呤能受体(P2Y12)激活,促进血小板活化并导致血栓炎症,增强炎症和损伤程度,加重炎症-凝血正反馈回路,进一步加重肺损伤。因此,白细胞介素-6受体(Interleukin-6 Recepor,IL-6R)、PAR4和P2Y12是干预炎症-凝血正反馈回路的关键靶点,通过阻断IL-6R预防炎症因子的产生和通过阻断PAR4和P2Y12抑制炎症-凝血正反馈回路在防治ALI的临床治疗和药物研制中具有重要意义。COVID-19 is a public health emergency that has spread globally. SARS-CoV-2 may infect cells through the S proteinACE2 pathway, causing tracheal epithelial cell damage and alveolar damage, further triggering inflammatory factor storms, and ultimately leading to ALI. Studies have shown that IL-6 is considered to be a key factor in the onset of lung injury cytokine storm in patients with COVID-19. Endothelial cell damage caused by inflammation can also lead to coagulation disorders, and further enhance the release of inflammatory factors, form a positive feedback loop of inflammation-coagulation, and aggravate lung injury. Secondly, the interaction between SARS-CoV-2 and ACE2 can cause angiotensin signal disorder, inflammation and tissue damage, etc., and activate PAR4 and P2Y12. The resulting acceleration of platelet activation and thrombotic inflammation enhances the degree of inflammation and damage, and exacerbates the inflammation-coagulation positive feedback loop, further aggravating lung injury. Therefore, IL-6R, PAR4 and P2Y12 are the key targets for interfering in the inflammation-coagulation positive feedback loop. Preventing the production of inflammatory factors by blocking IL-6R, and inhibiting the inflammation-coagulation positive feedback loop by blocking PAR4 and P2Y12 is of great significance in the clinical prevention and medicine development for ALI.

关 键 词：白细胞介素-6受体 蛋白酶活化受体4和嘌呤能受体 炎症-凝血正反馈回路 新型冠状病毒 急性肺损伤 

分 类 号：R563.1[医药卫生—呼吸系统]