筋骨痛消丸调控MLT/SIRT1介导的信号通路治疗膝骨关节炎模型大鼠的研究  

Jingu Tongxiao Pill Regulates the MLT/SIRT1 Signaling Pathway in the Treatment of Knee Osteoarthritis Model Rats

作　　者：刘源 李峰 史鹏博[2] 胡笑燊 郭珈宜 LIU Yuan;LI Feng;SHI Peng-bo;HU Xiao-shen;GUO Jia-yi(Luoyang Orthopedic-Traumatological Hospital of Henan Province(Henan Provincial Orthopedic Hospital),Luoyang Henan 471002;The First Affiliated Hospital of Henan University of Chinese Medicine,Zhegnzhou Henan 450000;School of Health Preservation and Rehabilitation,Chengdu University of Traditional Chinese Medicine,Chengdu Sichuan 610000)

机构地区：[1]河南省洛阳正骨医院(河南省骨科医院),河南洛阳471002 [2]河南中医药大学第一附属医院,河南郑州450000 [3]成都中医药大学养生康复学院,四川成都610000

出　　处：《世界中西医结合杂志》2024年第4期637-642,653,共7页World Journal of Integrated Traditional and Western Medicine

基　　金：国自然青年项目(82205239);中国博士后科学基金项目(2022M721066);河南省中医药科学研究专项课题项目(2023ZY2117);洛阳市科技发展计划项目(2022045Y)。

摘　　要：目的 观察筋骨痛消丸对膝骨关节炎(Knee osteoarthritis,KOA)模型大鼠软骨组织的影响,以及软骨组织中褪黑素(MLT)、沉默信息调节因子1(SIRT1)、基质金属蛋白酶3(MMP-3)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)表达的影响,研究筋骨痛消丸治疗KOA的机制,为临床运用筋骨痛消丸治疗KOA提供实验依据及理论基础。方法 将48只SPF级SD大鼠按随机数字表法分为空白组、模型组、双醋瑞因组、筋骨痛消丸组,每组各12只。筋骨痛消丸组造模成功后给予筋骨痛消丸汤剂灌胃干预,双醋瑞因组给予双醋瑞因灌胃干预,连续干预4周,干预结束后,观察比较各组大鼠干预前后患膝关节周围肿胀度;患膝软骨组织染色,并运用ELISA、Westernblot检测法检测各组大鼠软骨组织中褪黑素(Melatonin,MLT)、沉默信息调节因子1(Sirtuin 1,SIRT1)、白细胞介素-1β(Interleukin 1β,IL-1β)、基质金属蛋白酶-3(Matrix metalloproteinase-3,MMP-3)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)含量及蛋白质表达水平。结果 采用木瓜蛋白酶关节腔内注射的造模方法成功;药物干预的两组均可以有效改善膝骨关节炎大鼠的关节肿胀度(P<0.05);与模型组比较,筋骨痛消丸组在大鼠血清中MLT、SIRT1的含量及蛋白质表达水平明显升高(P<0.05)。结论 筋骨痛消丸可以促进软骨组织中MLT、SIRT1的表达水平,并降低IL-1β、MMP-3、TNF-α的含量,其治疗KOA作用机制可能是通过激活MLT/SIRT1介导的通路,抑制下游炎症因子释放来完成的。Objective To observe the effect of Jingu Tongxiao pill on the cartilage of knee osteoarthritis(KOA)model rats and the expression of melatonin(MLT),silence-information regulator 1(SIRT1),matrix metalloproteinase 3(MMP-3),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in the cartilage,and to study the mechanism of Jingu Tongxiao pill in the treatment of KOA,which will provide experimental basis and theoretical basis for the clinical application of Jingu Tongxiao pill in the treatment of KOA.Methods A total of 48 SPF-grade SD rats were randomly divided into blank group,model group,diacerein group and Jingu Tongxiao pill group according to random number table method,with 12 rats in each group.After successful modeling,the rats in Jingu Tongxiao pill group were given Jingu Tongxiao pill decoction by gavage and the rats in diacerein group were given diacerein by gavage for four weeks.At the end of the intervention,the swelling degree around the affected knee joint was compared before and after the intervention among all groups.The difference was observed by staining of the affected knee cartilage.The levels of MLT,SIRT1,IL-1 β,MMP-3 and TNF-αwere detected by ELISA and Western blot.Results The modeling method of intra-articular injection of papain was successful in this study.Both groups of drug intervention could effectively improve joint swelling in rats with KOA(P<0.05).Compared with the diacerein group,the content and protein expression levels of MLT and SIRT1 in the serum of rats in the Jingu Tongxiao pill group were significantly increased(P<0.05).Conclusion Jingu Tongxiao pill can promote the expression of MLT and SIRT1 in cartilage,and reduce the contents of IL-1 β,MMP-3 and TNF-α.Its mechanism in the treatment of KOA may be achieved by activating MLT/SIRT1 signaling pathway and inhibiting the release of downstream inflammatory factors.

关 键 词：筋骨痛消丸 平乐正骨 膝骨关节炎 褪黑素 沉默信息调节因子1 

分 类 号：R285.5[医药卫生—中药学]