中国比较医学杂志2025，Vol.35Issue(5)：12-23,12.DOI:10.3969/j.issn.1671-7856.2025.05.002
EV71通过Caspase-1/IL-1β信号通路诱导BALB/c乳鼠骨骼肌损伤
Enterovirus 71 induced skeletal muscle injury in BALB/c lactating mice via the caspase-1/interleukin-1β signaling pathway
摘要
Abstract
Objective To investigate the impact of enterovirus 71(EV71)on skeletal muscle injury and explore its mechanism in relation to the caspase-1/interleukin(IL)-1 β signaling pathway in EV71-induced skeletal muscle damage.Methods One-day-old BALB/c suckling mice were divided randomly into three groups:normal control(NC)(n=60),EV71 infection model(n=60),and caspase-1 inhibitor(EV71+VX765)(n=15)groups.The NC and EV71 model groups were further subdivided into four subgroups(5,7,10,and 14 days)(n=5 mice per group).An EV71-infected model was established by intraperitoneal injection of 25 × 103 μL/kg EV71 viral solution for 3 consecutive days.Mice in the caspase-1 inhibitor group received VX765(20 mg/kg)intraperitoneally 6 hours post-viral inoculation,continued daily for 10 days until sample collection.Mice in the NC group received an equivalent volume of saline containing 5％dimethylsulfoxide and 10％PEG300,followed by 2％cell maintenance solution after 6 hours.Post-modeling body weight and clinical disease scores were recorded.Pathological skeletal muscle damage was observed by hematoxylin-eosin(HE)staining,and expression levels of EV71 VP-1(viral capsid protein),pro-caspase-1,cleaved-caspase-1,IL-1 β,α-smooth muscle actin(SMA),and Collagen Ⅰ were detected by Western blot and immunofluorescence.Results Compared with the NC group at the same time points,mice in the EV71 model group exhibited reduced body weight,elevated disease scores,and skeletal muscle pathology characterized by inflammatory cell infiltration,myofiber dissolution,and decreased cross-sectional area(HE staining).Western blot showed significantly increased levels of EV71 VP-1,IL-1β,α-SMA,and Collagen Ⅰ in skeletal muscle homogenate from EV71 mice at 5,7,and 10 days post-infection(P＜0.001).In contrast,mice in the VX765 group showed improved body weight,reduced clinical scores(P＜0.01),and significant downregulation of EV71 VP-1(P＜0.01),pro-caspase-1,cleaved-caspase-1,IL-1β,and Collagen Ⅰ compared with the EV71 model group(P＜0.01).These findings were confirmed by immunofluorescence,indicating that inhibition of caspase-1 alleviated EV71-induced skeletal muscle injury.Conclusions EV71 may induce skeletal muscle injury by activating the caspase-1/IL-1β signaling pathway.关键词
EV71/BALB/c乳鼠/炎症/caspase-1/纤维化Key words
EV71/BALB/c suckling mice/inflammation/caspase-1/fibrosis引用本文复制引用
牛弘璘,杨木,曹琳,邹欣宏,陈雨菲,石国欣,刘蕾,王柏欣,崔国利..EV71通过Caspase-1/IL-1β信号通路诱导BALB/c乳鼠骨骼肌损伤[J].中国比较医学杂志,2025,35(5):12-23,12.基金项目
黑龙江省自然科学基金(LH2023H004) （LH2023H004）
佳木斯大学"东极"研究团队(DJXSTD202405). （DJXSTD202405）
