ngµç×ÓÓÎÏ·ÐÂÎÅÍøÑ¶£¨Í¨Ñ¶Ô±ÖÜÎÄÁ¼£©ÓÉÐÂÐ͹Ú×´²¡¶¾£¨severe acute respiratory syndrome coronavirus 2£¬£¬£¬SARS-CoV-2£©Ñ¬È¾ËùÒýÆðµÄÐÂÐ͹Ú×´²¡¶¾·ÎÑ×£¨Coronavirus disease 2019£¬£¬£¬COVID-19£©Òѵ¼ÖÂÈ«ÇòÁè¼Ý600ÍòÈËéæÃü£¬£¬£¬¶ÔÈËÀ࿵½¡ÓëÉç»á¿ªÕ¹Ôì³ÉÁËÆÆËðÐÔÓ°Ïì¡£¡£¡£¡£¡£È»¶ø£¬£¬£¬Õë¶ÔCOVID-19µÄÌØÒìÐÔÒ©ÎïÈÔ½Ïȱ·¦£¬£¬£¬ÆäÖ÷ÒªÔÒòÔÚÓÚÏÖÔÚ¶ÔSARS-CoV-2ÒýÆðºôÎüϵͳËðÉ˵ĻúÖÆÏàʶȱ·¦¡£¡£¡£¡£¡£
Ñ×Ö¢µÄʵÖÊÊÇÒ»ÖÖÃâÒß·ÀÓù·´Ó³£¬£¬£¬ËüÊÇ»úÌåÔÚÔâÊÜѬȾ»òΣÏÕÐԴ̼¤ºóËù¾ÙÐеı£»£»¤ÐÔ²½·¥¡£¡£¡£¡£¡£ÔÚºôÎüµÀ£¬£¬£¬Ñ×֢ͨ³£ÆðʼÓÚÉÏÆ¤Ï¸°û¶ÔÈëÇÖ²¡ÔÌåµÄʶ±ðÀú³Ì£¬£¬£¬¶Ôά³ÖºôÎüϵͳÎÈ̬ƽºâ¾ßÓÐÊ®·ÖÖ÷ÒªµÄÒâÒå¡£¡£¡£¡£¡£È»¶ø£¬£¬£¬Ñ×Ö¢·´Ó³Èôʧȥ¿ØÖÆ×ª»¯Îª³ÖÐø¶øÌ«¹ýµÄ²¡ÀíÐÔ·´Ó³£¬£¬£¬½«Ôì³ÉÑÏÖØµÄ²»Á¼Ð§¹û¡£¡£¡£¡£¡£Òò´Ë£¬£¬£¬ÉîÈë̽ÌÖ»úÌåÎÈ̬ʧºâÓëÑ×֢ǨÑÓ²»ÓúµÄ»úÖÆ£¬£¬£¬¾ßÓÐÖ÷ÒªµÄÀíÂÛÓëÁÙ´²×ª»¯ÒâÒå¡£¡£¡£¡£¡£
ÈÕǰ£¬£¬£¬ÖÜÎÄÁ¼½ÌÊÚÍŶÓÓëÖÓÄÏɽԺʿÍŶÓÏàÖú£¬£¬£¬ÔÚSARS-CoV-2Ö²¡»úÀí·½ÃæÈ¡µÃÖ÷ҪϣÍû¡£¡£¡£¡£¡£¸ÃÁªºÏÍŶÓʹÓõçÐÄÀíѧ¡¢¡¢·Ö×ÓÉúÎïѧ¡¢¡¢Ï¸°ûÉúÎïѧµÈʵÑéÊÖÒÕ£¬£¬£¬ÉîÈëÆÊÎöÁËϸ°ûÄÚÂÈÀë×Ó×÷Ϊ²¡ÀíÐÔµÚ¶þÐÅʹ½éµ¼ÁËCOVID-19ÆøµÀÑ×֢ǨÑÓ²»ÓúµÄ²¡Àí»úÖÆ£¬£¬£¬Ïà¹ØÑо¿Ð§¹ûÒÔ¡°SARS-CoV-2 nucleocapsid protein triggers hyperinflammation via protein-protein interaction-mediated intracellular Cl? accumulation in respiratory epithelium¡±ÎªÌâ½ÒÏþÔÚ×ÔÈ»³öÊ鼯ÍÅ£¨NPG£©ÆìϹú¼ÊȨÍþѧÊõÆÚ¿¯¡¶ÐźÅתµ¼Óë°ÐÏòÖÎÁÆ£¨Signal Transduction and Targeted Therapy£©¡·ÉÏ£¬£¬£¬²¢ÒÔµ±ÆÚ·âÃæ¹ÊÊÂչʾ¡£¡£¡£¡£¡£

ͼ1 Signal Transduction and Targeted Therapy 2022ÄêµÚ8ÆÚ·âÃæ
·âÃæÍ¼Æ¬½«ºôÎüµÀÉÏÆ¤Ï¸°ûÃè»æÎªÒ»¸öÌÒÔ´Ñþ³Ø£¬£¬£¬ÆäÖдú±íÂÈÀë×ӵĺÓÁ÷ͨÏ꾡°ûĤ³ÇǽÉϵÄÂÈÀë×ÓͨµÀCFTR´óÃÅÁ÷³ö£»£»µ±SARS-CoV-2ѬȾʱ£¬£¬£¬CFTR´óÃŹرգ¬£¬£¬´Ó¶øµ¼ÖÂÂÈÀë×Ó»ýÀÛ·ºÀÄÓëÑ×Ö¢·ç±©µÄ±¬·¢
¸ÃÑо¿ÒÔºôÎüµÀÉÏÆ¤Ï¸°ûÖêºÍÔ´ú×÷ÓýµÄÈ˺ôÎüµÀÉÏÆ¤Ï¸°ûΪÌåÍâÑо¿Ä£×Ó£¬£¬£¬Á¬ÏµÆøµÀÄÚµÎ×¢SARS-CoV-2²¡¶¾ÂѰ×Óë»î²¡¶¾¹¥¶¾µÄСÊóÔÚÌåÄ£×Ó£¬£¬£¬·¢Ã÷SARS-CoV-2ºËÒ¿ÇÂѰ׿ÉÓëËÞÖ÷ϸ°ûSmad3ÂѰ׻¥×÷£¬£¬£¬Í¨¹ýÕÙļmicroRNA-145½éµ¼ÂÈÀë×ÓͨµÀÄÒÐÔÏËά»¯¿çĤ´«µ¼µ÷ÀíÒò×Ó£¨cystic fibrosis transmembrane conductance regulator£¬£¬£¬CFTR£©µÄ±í´ïϵ÷£¬£¬£¬´Ó¶øÒÖÖÆÁË¿çÉÏÆ¤ÂÈÀë×ÓµÄÉøÍ¸»î¶¯¡£¡£¡£¡£¡£¼øÓÚÂÈÀë×ÓÉøÍ¸ÊÜ×èºÜ¿ÉÄܻᵼÖÂϸ°ûÄÚÂÈÀë×ÓÎÈ̬ʧºâ£¬£¬£¬¸ÃÑо¿½øÒ»²½Í¨¹ýÏÔ΢Àë×Ó³ÉÏñÊÖÒÕ£¬£¬£¬·¢Ã÷SARS-CoV-2ºËÒ¿ÇÂѰ״̼¤¿ÉÒýÆðºôÎüµÀÉÏÆ¤Ï¸°ûÄÚÂÈÀë×ÓŨ¶ÈÒì³£Éý¸ß£¬£¬£¬½ø¶øÍ¨¹ý¼¤»îÏÂÓεÄÂÈÀë×ÓÃô¸ÐÂѰסª¡ªÑªÇåÌÇÆ¤Öʼ¤Ëص÷Àí¼¤Ã¸1£¨serum glucocorticoid regulated kinase 1£¬£¬£¬SGK1£©½éµ¼NF-¦ÊBÐźÅͨ·»î»¯£¬£¬£¬ÓÕµ¼Ñ×Ö¢·´Ó³µÄ±¬·¢¡£¡£¡£¡£¡£ÁíÒ»·½Ã棬£¬£¬SARS-CoV-2ºËÒ¿ÇÂѰ׻¹¿ÉÒÔͨ¹ýNF-¦ÊBÒÀÀµµÄ;¾¶½éµ¼Á×Ëá¶þõ¥Ã¸4£¨phosphodiesterase 4£¬£¬£¬PDE4£©µÄ±í´ïÉϵ÷£¬£¬£¬½µµÍϸ°ûÄÚcAMPˮƽ£¬£¬£¬½øÒ»²½ÒýÆðCFTR¹Ø±Õ£¬£¬£¬´Ùʹϸ°ûÄÚÂÈÀë×ÓŨ¶Èά³ÖÔÚ¸ßˮƽ£¬£¬£¬´Ó¶øµ¼ÖÂÑ×Ö¢·´Ó³Ç¨ÑÓ²»Óú¡£¡£¡£¡£¡£ÓëÖ®Ïà·´£¬£¬£¬ÒÖÖÆ/ÇóýSGK1£¬£¬£¬»òÓèÒÔPDE4ÒÖÖÆ¼Á¸ÉÔ¤£¬£¬£¬¾ù¿ÉÒÔÏÔÖøÒÖÖÆSARS-CoV-2ºËÒ¿ÇÂѰ״̼¤ËùÒýÆðµÄ³ÖÐøÐÔÆøµÀÑ×Ö¢¡£¡£¡£¡£¡£

ͼ2 ϸ°ûÄÚÂÈÀë×Óµ÷¿ØSARS-CoV-2ËùÖºôÎüÉÏÆ¤Ñ×Ö¢·´Ó³µÄ»úÖÆÄ£Ê½
×ÛÉÏËùÊö£¬£¬£¬¸ÃÑо¿ÊÂÇéÊǹú¼Ê¹æÄ£ÄÚÂÊÏȱ¨µÀµÄϵͳÐÔÐðÊöϸ°ûÄÚÂÈÀë×Ó¼°ÆäÏÂÓÎÐźÅÍøÂçÔÚ²¡¶¾Ñ¬È¾ËùÖºôÎüϵͳËðÉËÖеÄ×÷ÓûúÖÆÑо¿£¬£¬£¬¶ÔCOVID-19µÄÐÂÒ©Ñз¢ÓëÖÎÁÆÕ½ÂÔ̽Ë÷¾ßÓÐÖ÷ÒªµÄÀíÂÛÖ¸µ¼ÒâÒå¡£¡£¡£¡£¡£
¸ÃÑо¿ÊÂÇéΪÖÜÎÄÁ¼½ÌÊÚÍŶӽüÄêÀ´ÏµÁÐÑо¿ÊÂÇéµÄÑÓÐøÐ§¹û¡£¡£¡£¡£¡£ÔÚ2015Äê½ÒÏþÓÚÃÀ¹ú¹ú¼Ò¿ÆÑ§ÔºÔº¿¯Proc Natl Acad Sci U S AµÄÂÛÎÄÖУ¬£¬£¬ÖÜÎÄÁ¼½ÌÊÚÓëÂ×ÕÕÈÙ½ÌÊÚÏàÖú£¬£¬£¬·¢Ã÷¸ÕµØ¹ÐγæÑ¬È¾¿ÉÒýÆðºôÎüµÀÉÏÆ¤Ï¸°ûÂÈÀë×ÓתÔËÊÜ×è[1]¡£¡£¡£¡£¡£ÔÚ2018Äê½ÒÏþÓÚNPGÆìÏÂÃâÒßѧ¹ú¼ÊȨÍþÆÚ¿¯Mucosal ImmunolµÄÂÛÎÄÖУ¬£¬£¬ÖÜÎÄÁ¼½ÌÊÚ¼°ÍŶÓÖ÷¸ÉÕÅÒÕÁÖÌØÆ¸¸±Ñо¿Ô±ÀÖ³ÉÅжϳöÁËÒ»ÖÖÐÂÐ͵ÄÂÈÀë×Ó¸ÐÓ¦ÂѰ×SGK1£¬£¬£¬²¢ÏµÍ³ÐԵزûÊÍÁËϸ°ûÄÚÂÈÀë×ÓÔÚϸ¾úѬȾËùÖÂÂýÐÔÆøµÀÑ×Ö¢ÐÔ¼²²¡£¡£¡£¡£¡£¨ÌØÊâÊÇÖ§Æø¹ÜÀ©ÕÅÖ¢£©ÖеÄÑ×Ö¢ÐźÅתµ¼×÷Óü°Æä·Ö×Ó»úÖÆ[2]¡£¡£¡£¡£¡£ÒÔºóÓÚ2019¡¢¡¢2021Äê»®·Ö½ÒÏþÓÚ¼ÄÉú³æÑ§¹ú¼ÊȨÍþÆÚ¿¯Int J ParasitolÓëPLoS Negl Trop DisµÄ2ƪÂÛÎÄÖУ¬£¬£¬¸ÃÑо¿ÍŶӽøÒ»²½ÑéÖ¤ÁËϸ°ûÄÚÂÈÀë×ÓÒì³£»£»ýÀÛÔÚÒõµÀëµÎ³æÑ¬È¾ËùÖÂÉúÖ³µÀÉÏÆ¤ËðÉËÖÐͬÑùʩչÁËÖ÷ÒªµÄ×÷ÓÃ[3-4]¡£¡£¡£¡£¡£Á¬Ïµ±¾Ñо¿Ð§¹û£¬£¬£¬Ï¸°ûÄÚÂÈÀë×ÓÒì³£ÀÛ»ýÆÕ±é±£´æÓÚ²¡ÔÌåѬȾµÄÀú³ÌÖУ¬£¬£¬ÕâΪ¸ÃÑо¿ÍŶÓËùÌá³öµÄϸ°ûÄÚÂÈÀë×Ó×÷Ϊ²¡ÀíÐÔµÚ¶þÐÅʹµÄ¿´·¨ÌṩÁ˼áʵµÄÀíÂÛÒÀ¾Ý¡£¡£¡£¡£¡£ÏìÓ¦µØ£¬£¬£¬ÒÔϸ°ûÄÚÂÈÀë×Ó¼°ÆäÏÂÓÎÐźÅÍøÂçΪ°ÐµãµÄÕ½ÂÔ»ò¿ÉΪ¶àÖÖÂýÐÔÑ×Ö¢ÐÔ¼²²¡µÄÖÎÁÆÌṩеÄ̽Ë÷Æ«Ïò¡£¡£¡£¡£¡£
¸ÃÑо¿ÂÛÎÄͨѶ×÷ÕßΪngµç×ÓÓÎÏ·ÉúÃü¿ÆÑ§Ñ§ÔºÖÜÎÄÁ¼½ÌÊÚ¡¢¡¢ÕÅÒÕÁÖÌØÆ¸¸±Ñо¿Ô±Óë¹ãÖݺôÎü¿µ½¡Ñо¿ÔºÖÓÄÏɽԺʿ¡£¡£¡£¡£¡£µÚÒ»×÷ÕßΪngµç×ÓÓÎÏ·ÉúÃü¿ÆÑ§Ñ§Ôº³ÂÀÚ¡¢¡¢Çñ׿¶û²©Ê¿¼°¹ãÖÝÒ½¿Æ´óѧ¹ØÎ°½ÜÑо¿Ô±¡¢¡¢Ð콨°î²©Ê¿¡£¡£¡£¡£¡£ngµç×ÓÓÎÏ·ÉúÃü¿ÆÑ§Ñ§ÔºÂ×ÕÕÈÙ½ÌÊÚ¡¢¡¢Ò¶¿ËÄѸ±½ÌÊÚΪ¸ÃÊÂÇéÌṩÁËÖ÷ÒªÖ§³Ö¡£¡£¡£¡£¡£±ðµÄ£¬£¬£¬ngµç×ÓÓÎÏ·ÉúÃü¿ÆÑ§Ñ§ÔºÁõ·å¸±½ÌÊÚΪ¸ÃÊÂÇéÖÐÂѰ×ÖÊ-ÂѰ×ÖÊ»¥×÷ʵÑéÌṩÁËÊÖÒÕÖ¸µ¼Òâ¼û¡£¡£¡£¡£¡£¸ÃÊÂÇé»ñµÃ¹ãÖݺôÎü¿µ½¡Ñо¿Ôº¿ª·Å¿ÎÌ⣨Öйúºã´ó¼¯ÍÅËùÌṩ×ʽð×ÊÖú£©¡¢¡¢¹ã¶«Ê¡ÖÓÄÏɽҽѧ»ù½ð»á¿ÆÑÐ×ÊÖú»ù½ð¼°¹ú¼Ò×ÔÈ»¿ÆÑ§»ù½ðµÈÏîÄ¿µÄ×ÊÖú¡£¡£¡£¡£¡£
ÂÛÎÄÁ´½Ó£ºhttps://www.nature.com/articles/s41392-022-01048-1
²Î¿¼ÎÄÏ×£º
[1] Guo HM, Gao JM, Luo YL, Wen YZ, Zhang YL, Hide G, Zhou WL, Ayala FJ, Lun ZR. Infection by Toxoplasma gondii, a severe parasite in neonates and AIDS patients, causes impaired anion secretion in airway epithelia. Proc Natl Acad Sci U S A. 2015 Apr 7; 112(14): 4435-40.
[2] Zhang YL, Chen PX, Guan WJ, Guo HM, Qiu ZE, Xu JW, Luo YL, Lan CF, Xu JB, Hao Y, Tan YX, Ye KN, Lun ZR, Zhao L, Zhu YX, Huang J, Ko WH, Zhong WD, Zhou WL, Zhong NS. Increased intracellular Cl? concentration promotes ongoing inflammation in airway epithelium. Mucosal Immunol. 2018 Jul; 11(4): 1149-1157.
[3] Xu JB, Zhang YL, Huang J, Lu SJ, Sun Q, Chen PX, Jiang P, Qiu ZE, Jiang FN, Zhu YX, Lai DH, Zhong WD, Lun ZR, Zhou WL. Increased intracellular Cl? concentration mediates Trichomonas vaginalis-induced inflammation in the human vaginal epithelium. Int J Parasitol. 2019 Aug; 49(9): 697-704.
[4] Xu JB, Lu SJ, Ke LJ, Qiu ZE, Chen L, Zhang HL, Wang XY, Wei XF, He S, Zhu YX, Lun ZR, Zhou WL, Zhang YL. Trichomonas vaginalis infection impairs anion secretion in vaginal epithelium. PLoS Negl Trop Dis. 2021 Apr 16; 15(4): e0009319.