湖南中医药大学学报2025,Vol.45Issue(4):617-623,7.DOI:10.3969/j.issn.1674-070X.2025.04.005
中等强度耐力运动对老年性骨质疏松症小鼠NLRP3/Caspase-1/GSDMD焦亡通路的影响
Effects of moderate-intensity endurance exercise on the NLRP3/Caspase-1/GSDMD pyroptosis pathway in mice with senile osteoporosis
摘要
Abstract
Objective To investigate the effects of moderate-intensity endurance exercise on senile osteoporosis(SOP)through the NOD-like receptor family pyrin domain containing protein 3(NLRP3)/cysteine protease-1(Caspase-1)/gasdermin D(GSDMD)signaling pathway.Methods Twenty-one 18-month-old male C57 mice were randomly divided into three groups:the 18-month-old group,the 20-month-old group,and the exercise group,with seven mice in each group.The SOP animal model was replicated using naturally aged male mice,and an additional seven six-month-old male C57 mice were selected as the young group.After one week of adaptive feeding,mice in the young group and 18-month-old group were euthanized for sample collection.Mice in the exercise group underwent moderate-intensity endurance training,while those in the 20-month-old group received no intervention.Samples were collected after eight weeks of intervention.Bone mineral density(BMD)of the left femur in each group of mice was measured using micro-computed tomography(Micro-CT).ELISA was used to determine the serum levels of bone metabolism markers,including C-terminal telopeptide of typeⅠ collagen(CTX-1),tartrate-resistant acid phosphatase(TRACP),N-terminal propeptide of typeⅠ procollagen(PINP),and bone-specific alkaline phosphatase(B-ALP).In addition,levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)in the right femur were assessed.Western blot analysis was conducted to determine the protein expression levels of NLRP3,Caspase-1,and the N-terminal fragment of GSDMD-N in the right femur of each group.Results Compared with the young group,the 18-month-old and 20-month-old groups showed increased serum levels of CTX-1 and TRACP,as well as elevated expression levels of NLRP3,Caspase-1,GSDMD-N,IL-1β,and IL-18 in the right femur(P<0.05,P<0.01).Meanwhile,serum levels of PINP and B-ALP,along with BMD of the left femur,decreased(P<0.05,P<0.01).Compared with the 18-month-old group,the 20-month-old group exhibited increases in serum CTX-1 and TRACP levels,as well as in NLRP3,Caspase-1,GSDMD-N,IL-1β,and IL-18 expression levels in the right femur(P<0.05,P<0.01),along with decreases in serum PINP and B-ALP levels and left femur BMD(P<0.05,P<0.01).Compared with the 20-month-old group,the exercise group showed reductions in serum CTX-1 and TRACP levels,as well as in right femoral expression levels of NLRP3,Caspase-1,GSDMD-N,IL-1β,and IL-18(P<0.05,P<0.01).Additionally,serum levels of PINP and B-ALP,and left femoral BMD increased(P<0.05,P<0.01).Conclusion Moderate-intensity endurance exercise can enhance bone mineral density and regulate bone metabolism in SOP mice,which may be related to the inhibiting NLRP3/Caspase-1/GSDMD signaling pathway,reducing inflammation,and pyroptosis levels.关键词
老年性骨质疏松症/耐力运动/炎症/焦亡/NLRP3/Caspase-1/GSDMDKey words
senile osteoporosis/endurance exercise/inflammation/pyroptosis/NLRP3/Caspase-1/GSDMD分类
临床医学引用本文复制引用
匡一瑾,周丹丹,周予婧,刘松涛,唐暹,佘艳,尹林玉,艾坤..中等强度耐力运动对老年性骨质疏松症小鼠NLRP3/Caspase-1/GSDMD焦亡通路的影响[J].湖南中医药大学学报,2025,45(4):617-623,7.基金项目
湖南省自然科学基金项目(2023JJ50411,2024JJ7533) (2023JJ50411,2024JJ7533)
湖南省卫健委卫生科研项目(B202303068776) (B202303068776)
湖南中医药大学校级科研项目(2024XJZC003) (2024XJZC003)
湖南中医药大学研究生创新课题(2024CX001). (2024CX001)