机构地区:[1]攀枝花学院医学院,攀枝花617000 [2]攀枝花学院康养学院,攀枝花617000
出 处:《病毒学报》2022年第4期814-820,共7页Chinese Journal of Virology
摘 要:NOD样受体热蛋白结构域相关蛋白3(Nod⁃like Receptor,Pyrin Domain Containing 3,NLRP3)炎症小体在炎症反应的调控中起重要作用,NLRP3炎症小体抑制剂MCC950能够减轻急性肺损伤小鼠的肺脏损伤。血球凝集素第1型、神经氨酸酶第1型(Hemagglutinin 1 Neuraminidase 1,H1N1)病毒FM1株感染引起小鼠巨噬细胞中NLRP3炎症小体激活,为了研究NLRP3炎症小体抑制剂MCC950对H1N1病毒感染模型小鼠肺脏的保护作用,本研究以ICR小鼠为对象,随机分为对照组、H1N1组、H1N1+MCC95组,H1N1组和H1N1+MCC95组通过H1N1病毒FM1株滴鼻的方式建立H1N1感染模型,H1N1+MCC95组给予MCC950腹腔注射干预、连续7d。检测支气管肺泡灌洗液(Bronchoalveolar lavage fluid,BALF)中白介素(IL)⁃1β、IL⁃18的含量,肺组织中H1N1病毒拷贝数、干重/湿重(W/D)、病理改变及NLRP3、凋亡相关斑点样蛋白(Apoptosis⁃asociated speck⁃like protein containing a CARD,ASC)、Cleaved caspase⁃1(Cysteinyl aspartate specific proteinase⁃1,含半胱氨酸的天冬氨酸蛋白水解酶⁃1)、GSDMD⁃N(Gasdermin D⁃N,消皮素D⁃N)的表达水平。结果显示,H1N1组小鼠肺组织出现了典型的病毒性肺炎病理改变,BALF中IL⁃1β、IL⁃18的含量及肺组织的H1N1病毒拷贝数、W/D、NLRP3、ASC、Cleaved caspase⁃1、GSDMD⁃N的表达水平均高于对照组(P<0.05);H1N1+MCC950组小鼠肺组织病毒性肺炎的病理改变明显改善,BALF中IL⁃1β、IL⁃18的含量及肺组织的H1N1病毒拷贝数、W/D、NLRP3、ASC、Cleaved caspase⁃1、GSDMD⁃N的表达水平均低于H1N1组(P<0.05)。以上结果表明H1N1病毒感染激活肺组织中NLRP3炎症小体抑制剂MCC950通过抑制炎症反应及细胞焦亡在H1N1病毒感染小鼠中发挥肺脏保护作用。The NLR family pyrin domain containing 3(NLRP3)inflammasome has an important role in regulation of the inflammatory response.An inhibitor of the NLRP3 inflammasome,MCC950,can alleviate acute lung injury in mice.We wished to study the protective effect of MCC950 on the lungs of H1N1 virus⁃infected mice.ICR mice were divided into three groups:control,H1N1,and H1N1+MCC950.The H1N1 group and H1N1+MCC950 group were used to establish a model of H1N1 infection by intranasal drip of the FM1 strain of the H1N1 virus,and MCC950 was injected(i.p.)for 7 days in the MCC950 group.The level of interleukin(IL)⁃1βand IL⁃18 in bronchoalveolar lavage fluid(BALF),the number of copies of the H1N1 virus,dry weight/wet weight(W/D),pathologic changes,and expression of NLRP3,ASC,cleaved caspase⁃1 and GSDMD⁃N in lung tissue were measured.The typical pathologic changes wrought by viral pneumonia were observed in the lung tissue of mice in the H1N1 group.The level of IL⁃1βand IL⁃18 in BALF,number of copies of the H1N1 virus,W/D,and expression of NLRP3,ASC,cleaved caspase⁃3,and GSDMD⁃N in the lung tissue of mice in the H1N1 group were higher than those of the control group(P<0.05).The pathologic changes of viral pneumonia in the lung tissue of mice in the H1N1+MCC950 group were improved significantly,the level of IL⁃1βand IL⁃18 in BALF,the number of copies of the H1N1 virus,W/D,and expression of NLRP3,ASC,cleaved caspase⁃3,GSDMD⁃N in the lung tissue of mice in the H1N1+MCC950 group were significantly lower than those in the H1N1 group(P<0.05).These results indicated that infection with the H1N1 virus activated the NLRP3 inflammasome in lung tissue,and that MCC950 has a protective role in the lungs of H1N1 virus⁃infected mice because it can inhibit the inflammatory response and pyroptosis.
关 键 词:病毒性肺炎 H1N1病毒 NLRP3炎症小体 炎症反应 细胞焦亡
分 类 号:R373.13[医药卫生—病原生物学]
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