| 引用本文: |
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[点击复制] |
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| 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 |
| 匡一瑾,周丹丹,周予婧,刘松涛,唐暹,佘艳,尹林玉,艾坤 |
| (湖南中医药大学针灸推拿与康复学院, 湖南 长沙 410208;湘南学院附属医院康复医学科, 湖南 郴州 423000) |
| 摘要: |
| 目的 基于类NOD样受体家族含吡啶结构域蛋白3（NLRP3）/半胱氨酸蛋白酶-1（Caspase-1）/气孔蛋白D（GSDMD）信号通路探索中等强度耐力运动抗老年性骨质疏松症（SOP）的作用。方法 将21只18月龄雄性C57小鼠随机分为18月龄组、20月龄组、运动组，每组7只，采用自然衰老的雄性小鼠复制SOP动物模型，另取7只6月龄雄性C57小鼠作为青年组。青年组和18月龄组在适应性喂养1周后处死并取材，运动组小鼠进行中等强度耐力运动，20月龄组不作任何处理，干预8周后取材。采用Micro-CT检测各组小鼠左侧股骨骨密度（BMD），ELISA检测各组小鼠血清骨代谢标志物Ⅰ型胶原C端肽（CTX-1）、抗酒石酸酸性磷酸酶（TRACP）、I型前胶原氨基端前肽（PINP）、特异性碱性磷酸酶B(B-ALP)水平及右侧股骨白细胞介素-1β（IL-1β）、白细胞介素-18（IL-18）含量变化，Western blot检测各组小鼠右侧股骨中NLRP3、Caspase-1、气孔蛋白D的N端片段（GSDMD-N）蛋白表达水平。结果 与青年组比较，18月龄组和20月龄组血清CTX-1、TRACP，右侧股骨NLRP3、Caspase-1、GSDMD-N、IL-1β、IL-18表达水平均升高（P＜0.05，P＜0.01），血清PINP、B-ALP和左侧股骨BMD均降低（P＜0.05，P＜0.01）；与18月龄组比较，20月龄组血清CTX-1、TRACP和右侧股骨NLRP3、Caspase-1、GSDMD-N、IL-1β、IL-18表达水平均升高（P＜0.05，P＜0.01），血清PINP、B-ALP和左侧股骨BMD均降低（P＜0.05，P＜0.01）；与20月龄组相比，运动组血清CTX-1、TRACP，右侧股骨NLRP3、Caspase-1、GSDMD-N、IL-1β、IL-18表达水平均降低（P＜0.05，P＜0.01），血清PINP、B-ALP和左侧股骨BMD均升高（P＜0.05，P＜0.01）。结论 中等强度耐力运动可提高SOP小鼠的骨密度、调节骨代谢，这一作用可能与其抑制NLRP3/Caspase-1/GSDMD信号通路、降低炎症和焦亡水平有关。 |
| 关键词: 老年性骨质疏松症 耐力运动 炎症 焦亡 NLRP3 Caspase-1 GSDMD |
| DOI：10.3969/j.issn.1674-070X.2025.04.005 |
| 投稿时间：2024-12-09 |
| 基金项目:湖南省自然科学基金项目（2023JJ50411,2024JJ7533）；湖南省卫健委卫生科研项目（B202303068776）；湖南中医药大学校级科研项目（2024XJZC003）；湖南中医药大学研究生创新课题（2024CX001）。 |
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| Effects of moderate-intensity endurance exercise on the NLRP3/Caspase-1/GSDMD pyroptosis pathway in mice with senile osteoporosis |
| KUANG Yijin, ZHOU Dandan, ZHOU Yujing, LIU Songtao, TANG Xian, SHE Yan, YIN Linyu, AI Kun |
| (School of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Department of Rehabilitation Medicine, Affiliated Hospital of Xiangnan University, Chenzhou, Hunan 423000, China) |
| 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. |
| Key words: senile osteoporosis endurance exercise inflammation pyroptosis NLRP3 Caspase-1 GSDMD |
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