天津中医药大学学报2026，Vol.45Issue(4)：444-450,7.DOI:10.11656/j.issn.1673-9043.2026.04.10
电针调控MLT/cAMP/PKA/CREB信号通路影响膝骨性关节炎兔软骨损伤及炎症反应机制研究
Effects of electroacupuncture on cartilage damage and inflammatory response in rabbits with knee osteoarthritis by modulating the MLT/cAMP/PKA/CREB signaling pathway
摘要
Abstract
[Objective]To observe the therapeutic effect of electroacupuncture on rabbits with knee osteoarthritis(KOA)and its effects on the melatonin(MLT),cyclic adenosine monophosphate(cAMP),protein kinase A(PKA),and cAMP response element-binding protein(CREB)pathway,and to explore the possible mechanism of electroacupuncture in treating knee osteoarthritis.[Methods]New Zealand rabbits were randomly divided into sham operation group,model group,and treatment group,with 6 rabbits in each group.The right knee KOA model was established using the traditional Hulth method.In the treatment group,electroacupuncture was applied to the right"Dubi"(ST35),"Neixiyan"(EX-LE4),"Zusanli"(ST36),"Xuehai"(SP10),and"Yanglingquan"(GB34)acupoints with sparse-dense waves at a frequency of 6 Hz/15 Hz and intensity of 2 mA,20 min per session,once daily for 28 consecutive days.After intervention,the Lequesne MG score was used to assess the behavioral performance of the three groups.Hematoxylin-eosin(HE)and Safranin O-Fast green staining were used to observe pathological changes in knee joint cartilage and to calculate the Mankin's score.ELISA was used to determine the serum level of MLT,the cartilage content of cAMP,and the concentration of matrix metalloproteinase-13(MMP-13)in joint fluid.Quantitative real-time PCR(qRT-PCR)was used to detect the mRNA expression of arylalkylamine N-acetyltransferase(AANAT)in the rabbit pineal gland,and of melatonin receptor 1(MT1)and melatonin receptor 2(MT2)in cartilage.Western blot was used to detect the expression of proteins in the PKA/CREB signaling pathway in chondrocytes.[Results]Compared with the sham operation group,the model group showed significantly higher Lequesne MG and Mankin's scores(P<0.001),higher MMP-13 level(P<0.001),higher AANAT level(P=0.073),and higher MT1(P=0.009)and MT2(P=0.011)levels,while the expression of cAMP(P<0.001),PKA(P<0.001),and CREB(P=0.004)and the concentration of MLT(P=0.002)were decreased.Compared with the model group,the treatment group showed significantly lower Lequesne MG and Mankin's scores(P<0.001),significantly decreased MMP-13 level(P<0.001),increased MLT(P=0.014)and AANAT(P=0.024)levels,and increased expression of MT1(P=0.004),MT2(P<0.001),cAMP(P<0.001),PKA(P=0.045),and CREB(P=0.024).Compared with the sham operation group,the model group exhibited chondrocyte aggregation,fissuring,irregular arrangement,blurred tide lines,and exposed subchondral bone tissue.Compared with the model group,the treatment group showed significantly reduced cartilage pathological damage.[Conclusion]Electroacupuncture can significantly improve articular cartilage degeneration and knee pain,and the mechanism may be related to activation of the MLT/cAMP/PKA/CREB signaling pathway by electroacupuncture.关键词
电针/膝骨性关节炎/褪黑素/环磷酸腺苷/蛋白激酶A/环磷酸腺苷响应元件结合蛋白/炎症Key words
electroacupuncture/knee osteoarthritis/MLT/cAMP/PKA/CREB/inflammation分类
医药卫生引用本文复制引用
韩金昌,于曼,周鑫,杨光,符碧峰,王平,张超..电针调控MLT/cAMP/PKA/CREB信号通路影响膝骨性关节炎兔软骨损伤及炎症反应机制研究[J].天津中医药大学学报,2026,45(4):444-450,7.基金项目
天津市教委科研计划项目(2022KJ165,2023KJ152). （2022KJ165,2023KJ152）
