摘要
目的:探究有氧运动经Janus激酶3(JAK3)-信号转导及转录激活因子5α(STAT5α)信号通路对SAMP8小鼠的影响,为有氧运动抗炎性衰老提供新思路。方法:将16只28周龄快速衰老SAMP8小鼠随机分为模型(Mod)组和运动(Exe)组,每组8只;另取8只同龄正常衰老SAMR1小鼠为对照(Con)组。Exe组小鼠通过跑台方式进行有氧训练8周。观测各组小鼠毛发及体重变化、免疫器官指数、免疫器官组织形态学改变、脾脏衰老标志物P16表达量变化,以及血清及脾脏炎症因子[肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)]和衰老指标IL-2浓度;脾脏IL-2、JAK3和STAT5αmRNA及蛋白表达变化情况。结果:(1)与Con组相比,Mod组小鼠毛发光泽度降低,发量减少,部分甚至出现斑秃;体重增加;脾脏指数与胸腺指数均显著下降(P<0.01);免疫器官出现明显萎缩衰老;血清及脾脏衰老指标IL-2浓度显著降低(P<0.01),脾脏衰老标志物P16浓度显著增加(P<0.01);血清及脾脏炎症因子TNF-α和IL-1β显著升高(P<0.01);脾脏IL-2 mRNA表达显著降低(P<0.01),IL-2受体γ亚基(IL-2RG)mRNA表达明显下降(P<0.01),JAK3和STAT5αmRNA表达显著升高(P<0.01);脾脏IL-2蛋白表达显著降低(P<0.01),STAT5α蛋白表达显著升高(P<0.01),JAK3蛋白表达明显升高(P<0.01)。(2)与Mod组相比,Exe组毛发相对旺盛,毛发光泽度较好;体重偏低;脾脏指数和胸腺指数显著升高(P<0.01);免疫器官衰老程度得到延缓;血清及脾脏衰老指标IL-2浓度显著性升高(P<0.05),脾脏衰老标志物P16浓度显著性降低(P<0.001);血清及脾脏炎症因子TNF-α和IL-1β显著性降低(P<0.05);脾脏IL-2和IL-2RG mRNA表达显著增高(P<0.05),JAK3和STAT5αmRNA表达显著降低(P<0.05);IL-2蛋白表达显著增高(P<0.05),STAT5α和JAK3蛋白表达显著下降(P<0.01)。结论:有氧运动可延缓小鼠炎性衰老,JAK3-STAT5α可能为其具体作用途径。
AIM:To investigate the mechanism through which aerobic exercise improves inflammatory senes‑cence in SAMP8 mice via Janus kinase 3(JAK3)-signal transducer and activator of transcription 5α(STAT5α)signaling pathway and to provide novel insights for anti-inflammatory aging interventions.METHODS:Sixteen 28-week-old SAMP8 mice were randomly divided into model(Mod)group and exercise(Exe)group,with 8 mice in each group.Addi‑tionally,8 senile SAMR1 mice served as control(Con)group.The mice in Exe group underwent an 8-week aerobic training regimen on a treadmill.We monitored the changes in hair quality and body weight,immune organ indexes,histomorpho‑logical alterations in immune organs,the expression levels of spleen aging marker P16,and the serum and spleen levels of inflammatory factors[tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)]and aging indicator IL-2.Moreover,we examined the alterations in the mRNA and protein expression of IL-2,JAK3 and STAT5αin the spleen.RESULTS:(1)Compared with Con group,the mice in Mod group exhibited decreased hair luster and volume,with some instances of alopecia areata,increased body weight,markedly reduced spleen and thymus indexes,evident atrophy and senescence of immune organs,and markedly decreased concentration of IL-2 in the serum and spleen.The expression of P16 in the spleen,and the serum and spleen levels of inflammatory factors TNF-αand IL-1βwere significantly increased.The mRNA expression of IL-2 and IL-2 receptor subunit gamma(IL-2RG)in the spleen was markedly decreased,whereas that of JAK3 and STAT5αwas markedly increased.Furthermore,the protein expression of IL-2 in the spleen was markedly de‑creased,whereas that of STAT5αand JAK3 was markedly increased.(2)Compared with Mod group,the mice in Exe group showed relatively vigorous hair growth and better hair luster,lower body weight,markedly increased spleen and thy‑mus indexes,and delayed immune organ aging.The concentration of IL-2 in the serum and spleen was markedly in‑creased,while the expression of P16 in the spleen was markedly decreased.The levels of TNF-αand IL-1βin the serum and spleen were markedly decreased.The mRNA expression of IL-2 and IL-2RG in the spleen was markedly increased,whereas that of JAK3 and STAT5αwas markedly decreased.The protein levels of IL-2 were markedly increased,whereas those of STAT5αand JAK3 were markedly decreased.CONCLUSION:Aerobic exercise can delay inflammatory aging in mice possibly through the JAK3-STAT5αsignaling pathway.
作者
钱艳
卢蕊
张燕
梁隆钰
夏雨
丁海丽
QIAN Yan;LU Rui;ZHANG Yan;LIANG Longyu;XIA Yu;DING Haili(Chengdu Sport University,Chengdu 641418,China;General Hospital of Western Theater Command,Chengdu 610041,China)
出处
《中国病理生理杂志》
北大核心
2025年第8期1589-1595,共7页
Chinese Journal of Pathophysiology
基金
四川省自然科学基金资助项目(No.2025ZNSFSC1596,No.2023NSFSC0545)
四川省科技创新创业苗子工程重点项目(No.2023JDRC0100)
运动医学四川省重点实验室(No.2021-A030)。
作者简介
通讯作者:丁海丽,E-mail:dinghaili@cdsu.edu.cn。
