李朋 李钊 罗天 胡仕畅 霍少川

摘要 目的：探討ERRα/SOX9信号通路在绝经后妇女不同证型膝骨关节炎（KOA）关节软骨中的作用。方法：选取2018年6月至2019年4月广州中医药大学第三附属医院收治的绝经后KOA患者，根据中医证型标准分为风寒湿痹证、风湿热痹证、瘀血闭阻证和肝肾亏虚证4组，采用RT-PCR和Western Blot检测ERRα/SOX9信号通路表达情况。结果：各组间膝关节软骨组织ERRα、SOX9和Col2α1表达量比较差异有统计学意义（P<0.05）。与风寒湿痹组比较，风湿热痹组ERRα、SOX9和Col2α1表达量之间差异无统计学意义（P>0.05）;瘀血痹阻组ERRα表达量升高，SOX9、Col2α1表达量降低（P<0.05）;肝肾亏虚组ERRα、Col2α1表达量降低（P<0.05），SOX9表达量升高（P<0.05）。与风湿热痹组比较，瘀血痹阻组ERRα表达量升高，SOX9、Col2α1表达量降低（P<0.05）;肝肾亏虚组ERRα、Col2α1表达量降低（P<0.05），SOX9表达量升高（P<0.05）。与瘀血痹阻组比较，肝肾亏虚组ERRα、Col2α1表达量降低（P<0.05）;SOX9表达量升高（P<0.05）。结论：绝经后妇女不同中医证型KOA患者关节软骨组织ERRα/SOX9信号通路存在差异，揭示不同证型ERRα/SOX9信号通路的差异将为中医药辨证施治绝经后KOA提供理论基础。

关键词 膝骨关节炎;ERRα/SOX9信号通路;绝经后妇女;关节软骨;中医辨证分型;

Analysis of ERR a /SOX9 Signaling Pathway in Articular Cartilage of Postmenopausal

with Different Traditional Chinese Medicine Syndromes of Knee Osteoarthritis

LI Peng1，LI Zhao1，LUO Tian1，HU Shichang2，HUO Shaochuan3

（1 Third Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine，Guangzhou 510240，China;

2 Guangzhou University of Traditional Chinese Medicine，Guangzhou 510450，China; 3 The First Affiliated

Hospital of Guangzhou University of Chinese Medicine，Guangzhou 510405，China）

Abstract Objective：To investigate the role of ERRa /SOX9 signaling pathway in postmenopausal women with different types of knee osteoarthritis articular cartilage.Methods：Postmenopausal KOA patients admitted to Third Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine were selected as the research objects and were divided into 4 groups according to TCM syndrome type criteria：wind-cold-dampness arthralgia syndrome，wind-dampness-heat arthralgia，blood stasis arthralgia syndrome，and liver-kidney deficiency syndrome.Rt-pcr and Western Blot were used to detect the ERR alpha /SOX9 signal pathway expression.Results：The difference of ERR-alpha，SOX9 and Col2-alpha-1 expression was statistically significant（P<0.05）.Compared with wind-cold-dampness arthralgia group，there was no statistically significant difference in the expression of ERRα，SOX9 and Col2α1 in wind-dampness-heat arthralgia groups（P<0.05）.Compared with the blood stasis arthralgia瘀血痹阻 group，there was no significant difference in the expression of ERRα，SOX9 and Col2α1 in the wind-dampness-heat arthralgia group（P>0.05）; the expression of ERRα increased in the blood stasis arthralgia group，and the expression of SOX9 and Col2α1 decreased（P<0.05）; the expression of ERRα and Col2α1 in the liver and kidney deficiency group decreased（P<0.05），and the expression of SOX9 increased（P<0.05）.Compared with the wind-dampness-heat arthralgia，the expression of ERRα in the blood stasis arthralgia increased，and the expression of SOX9 and Col2α1 decreased（P<0.05）; the expression of ERRα and Col2α1 in the liver and kidney deficiency group decreased（P<0.05），and the expression of SOX9 increased（P<0.05）.Compared with blood stasis arthralgia group，the expression of ERRα and Col2α1 in the liver and kidney deficiency group decreased（P<0.05）; the expression of SOX9 increased（P<0.05）.Conclusion：There are differences in the ERR alpha /SOX9 signaling pathways in the articular cartilage of postmenopausal women with different TCM syndromes of KOA.The discovery of the differences in the ERR alpha /SOX9 signaling pathways between different syndroms of KOA provides a theoretical basis for TCM syndrome differentiation in the treatment of post-menopausal KOA.

Keywords Knee Osteoarthritis; ERR a /SOX9 signaling pathway; Postmenopausal; Articular cartilage; TCM syndrome differentiation

中图分类号：R271.9;R274.9;R274.32文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.02.027

膝骨关节炎（Knee Osteoarthritis，KOA）是一种以膝关节疼痛、关节僵硬、活动受限甚至关节畸形为主要临床症状，是以膝关节的关节软骨损伤、关节软骨下骨外露、关节骨赘生成、关节间隙变窄等为病理改变的膝关节退行性疾患，也是中老年人的常见病和多发病，其发病率随年龄增长逐渐升高，在中国，从40岁开始发病率逐渐升高，60～70岁达到高峰，65岁及以上的老年人发病率高达75%[1-2]。其主要表现为双侧膝关节疼痛和僵硬、关节肿胀和变形、股四头肌无力和消瘦等症状和体征，严重影响患者生活和工作[3]。KOA属中医“痹证”范畴，依据“国家中医药管理局‘十一五重点专科协作组膝痹病（膝关节骨性关节炎）诊疗方案[4]将KOA分为风寒湿痹证、风湿热痹证、瘀血闭阻证和肝肾亏虚证，不同证型膝关节疼痛程度具有差异性[5]，且血清炎性反应指标表达量也存在差异[6]。妇女绝经后雌激素水平降低，改变了骨与软骨代谢，继而引发关节软骨退变加速，导致KOA发病率明显增加[7]。……