基于PPARγ/NF-κB信号通路探讨防己黄芪消肿方干预代谢综合征表型骨关节炎作用机制  

Discussion on the Mechanism of Intervention of Fangji Huangqi Xiaozhong Prescription in Metabolic Syndrome Phenotype Osteoarthritis Based on PPARγ/NF-κB Signaling Pathway

作　　者：危一飞 李紫阁 白天宇 邱佳明 王宏杰 肖潇 温冠楠 梁佩文 程桯[1,4] WEI Yifei;LI Zige;BAI Tianyu;QIU Jiaming;WANG Hongjie;XIAO Xiao;WEN Guannan;LIANG Peiwen;CHENG Ting(Wangjing Hospital,China Academy of Chinese Medical Sciences,Beijing 100102,China;Beijing First Integrated Traditional Chinese and Western Medicine Hospital,Beijing 100020,China;Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University,Beijing 100010,China;Beijing Key Laboratory of Traditional Chinese Medicine Orthopedic Technology,Beijing 100102,China)

机构地区：[1]中国中医科学院望京医院,北京100102 [2]北京市第一中西医结合医院,北京100020 [3]首都医科大学附属北京中医医院,北京100010 [4]中医正骨技术北京市重点实验室,北京100102

出　　处：《中国中医药信息杂志》2024年第8期76-83,共8页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：中国中医科学院望京医院基础研究苗圃培育计划(WJYY-YJKT-2022-08);国家自然科学基金青年科学基金(82305277);首都卫生发展科研专项(首发-2022-2-4162);中国中医科学院骨伤科学重大攻关项目(CI2021A02001);中国中医科学院高水平中医医院建设项目(WJZJ-202322)。

摘　　要：目的基于PPARγ/NF-κB信号通路探究防己黄芪消肿方对代谢综合征表型骨关节炎(MS-OA)大鼠的治疗作用及机制。方法SD大鼠随机分为假手术组、骨关节炎(OA)组、MS-OA组、西药组和中药高、低剂量组,采用改良Hulth法建立OA模型,改良Hulth法+高碳水高脂肪饮食建立MS-OA模型。中药高、低剂量组分别予防己黄芪消肿方药液15.12、7.56 g/kg灌胃,西药组给予洛索洛芬钠16.2 mg/kg灌胃,其余组予生理盐水灌胃,每日1次,连续6周。测量大鼠体质量,生化检测血脂及血糖,ELISA检测血清肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-10及瘦素含量,番红O-固绿及HE染色观察软骨组织形态,免疫组化染色检测软骨组织蛋白聚糖(Acan)、Ⅹ型胶原(ColⅩ)、基质金属蛋白酶13(MMP13)、TNF-α、IL-1β、过氧化物酶体增殖物激活受体γ(PPARγ)表达,Western blot检测软骨组织PPARγ、核因子(NF)-κBp65、p-NF-κBp65蛋白表达。结果与假手术组比较,MS-OA组大鼠体质量及血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、TNF-α、IL-1β、瘦素含量均升高(P<0.01),高密度脂蛋白胆固醇(HDL-C)、IL-10含量降低(P<0.01),软骨组织退变明显,Mankin评分增加(P<0.01),软骨组织ColⅩ、MMP13、TNF-α、IL-1β、p-NF-κBp65蛋白表达升高(P<0.05,P<0.01),Acan、PPARγ蛋白表达降低(P<0.01);与MS-OA组比较,中药高剂量组大鼠血清TC、TG、LDL-C、TNF-α、瘦素含量降低(P<0.05,P<0.01),IL-10含量增加(P<0.05),软骨组织病理损伤改善,Mankin评分降低(P<0.01),软骨组织ColⅩ、MMP13、TNF-α、IL-1β、p-NF-κBp65蛋白表达降低(P<0.05,P<0.01),Acan、PPARγ蛋白表达升高(P<0.01,P<0.05)。结论防己黄芪消肿方可改善MS-OA大鼠脂代谢紊乱、改善关节内炎症环境、平衡软骨代谢、延缓软骨退变,其作用机制可能与调节PPARγ/NF-κB信号通路有关。Objective To explore the treatment effects and mechanism of Fangji Huangqi Xiaozhong Prescription in metabolic syndrome phenotype osteoarthritis(MS-OA)based on PPARγ/NF-κB signaling pathway.Methods SD rats were randomly divided into sham-operation group,OA group,MS-OA group,Western medicine group,and TCM high-and low-dasage groups.The modified Hulth method was used to make the OA model,and OA model was added with high-carbohydrate high-fat diet to make the MS-OA model.TCM high-and low-dosage groups were given 15.12,7.56 g/kg Fangji Huangqi Xiaozhong Prescription for gavage.The Western medicine group was given 16.2 mg/kg of losoprofen sodium by gavage,while the other groups were given physiological saline by gavage once a day for 6 consecutive weeks.Rat body mass was measured,biochemical detection of blood lipids and blood glucose was conducted,ELISA was used to detect the contents of serum TNF-α,IL-1β,IL-10 and leptin,morphological changes in cartilage tissue were observed using safranin O-fixed green and HE staining,immunohistochemical staining was used to detect expressions of Acan,ColⅩ,MMP13,TNF-α,IL-1βand PPARγin cartilage tissue,Western blot was used to detected the expression of PPARγ,NF-κBp65 and p-NF-κBp65 protein in cartilage tissue.Results Compared with the sham-operation group,body mass and serum TC,TG,LDL-C,TNF-α,IL-1βand leptin of MS-OA group increased significantly(P<0.01),the contents of HDL-C and IL-10 decreased(P<0.01),cartilage tissue degeneration was significant,and the Mankin score increased(P<0.01),the expression of ColⅩ,MMP13,TNF-α,IL-1β,p-NF-κBp65 protein increased(P<0.05,P<0.01),and the expression of Acan and PPARγprotein decreased(P<0.01).Compared with the MS-OA group,the contents of serum TC,TG,LDL-C,TNF-αand leptin decreased in TCM high-dosage group(P<0.05,P<0.01),the content of IL-10 increased(P<0.05),the pathological damage of cartilage tissue improved,the Mankin score decreased(P<0.01),the expressions of ColⅩ,MMP13,TNF-α,IL-1βand p-NF-κBp65 protein in cartil

关 键 词：防己黄芪消肿方 骨关节炎 代谢综合征 PPARγ/NF-κB信号通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]