北京中医药大学学报2024，Vol.47Issue(8) ：1111-1118.DOI:10.3969/j.issn.1006-2157.2024.09.012

对膝骨关节炎肝肾亏虚证和痰瘀互结证患者关节液中MMP-13、TGF-β1含量及关节软骨中Smad3磷酸化的研究

Study of MMP-13 and TGF-β1 in synovial fluid and P-Smad3 in articular cartilage of patients with knee osteoarthritis of liver-kidney deficiency pattern and pattern of intermingled phlegm and blood stasis

刘雨煊 刘向春 亓建 陈婧 刘勤哲 王乾顺 吕天成 蓝典 叶超
北京中医药大学学报2024，Vol.47Issue(8) ：1111-1118.DOI:10.3969/j.issn.1006-2157.2024.09.012
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对膝骨关节炎肝肾亏虚证和痰瘀互结证患者关节液中MMP-13、TGF-β1含量及关节软骨中Smad3磷酸化的研究

Study of MMP-13 and TGF-β1 in synovial fluid and P-Smad3 in articular cartilage of patients with knee osteoarthritis of liver-kidney deficiency pattern and pattern of intermingled phlegm and blood stasis

刘雨煊 1刘向春 1亓建 1陈婧 2刘勤哲 1王乾顺 1吕天成 1蓝典 1叶超1
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作者信息

  • 1. 北京中医药大学东直门医院 北京 100700
  • 2. 北京中医药大学第三附属医院
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摘要

目的 比较膝骨关节炎肝肾亏虚证和痰瘀互结证患者关节液中基质金属蛋白酶13(MMP-13)和转化生长因子-β1(TGF-β1)的含量、关节软骨Smad3磷酸化(P-Smad3)程度及其与证候的相关性.方法 采用横断面现场调查研究的方法,收集2019年9月—2023年2月于北京中医药大学东直门医院骨伤科住院的膝骨关节炎患者.共纳入112例膝骨关节炎患者,其中,肝肾亏虚证63例、痰瘀互结证49例.分别利用视觉模拟评分法(VAS)、Lysholm膝关节评分量表及Kellgren-Lawrence(K-L)分级标准对膝关节疼痛强度、功能及影像学结果进行量化;应用中医证候评分量表辨识及量化证候;以免疫组化法测定关节软骨Smad3磷酸化特点,ELISA测定关节液MMP-13和TGF-β1含量,然后分析其水平特点及其与证候程度间的相关性.结果 ①膝骨关节炎肝肾亏虚证与痰瘀互结证患者VAS评分、Lysholm评分、K-L分级差异无统计学意义.②与痰瘀互结证患者比较,肝肾亏虚证患者关节液MMP-13含量较高,而关节液TGF-β1含量较低(P<0.05).③肝肾亏虚证患者关节液MMP-13含量与中医证候评分呈正相关性(r=0.292,P=0.020),关节液TGF-β1含量与中医证候评分呈负相关性(r=-0.781,P<0.001);痰瘀互结证患者关节液MMP-13含量与中医证候评分呈正相关性(r=0.936,P<0.001).④膝骨关节炎肝肾亏虚证患者关节软骨P-Smad3表达低于痰瘀互结证患者(P<0.05).结论 膝骨关节炎肝肾亏虚证和痰瘀互结证患者关节液TGF-β1、MMP-13含量和P-Smad3表达不同,与不同证候下的病因病机分析相一致.肝肾亏虚证患者关节液TGF-β1、MMP-13水平可以在一定程度上反映证候的严重程度,其作用机制可能与TGF-β/Smad信号通路激活水平受到抑制有关,此研究丰富了证候基础的研究内容.

Abstract

Objective We aimed to compared matrix metalloproteinase-13 (MMP-13) and transforming growth factor-β1 (TGF-β1) in synovial fluid,the phosphorylation level of Smad3 in articular cartilage (P-Smad3),and their correlation with traditional Chinese medicine (TCM) patterns in patients with knee osteoarthritis (KOA) of liver-kidney deficiency pattern and pattern of intermingled phlegm and blood stasis.Methods Using a cross-sectional field investigation method,KOA patients hospitalized in the Orthopedics Department of Dongzhimen Hospital,Beijing University of Chinese Medicine from September 2019 to February 2023 were collected. A total of 112 KOA patients were included,among which 63 cases were diagnosed with liver-kidney deficiency pattern,and 49 cases were diagnosed with pattern of intermingled phlegm and blood stasis. The intensity of knee pain,function,and X-ray imaging result were quantified using the Visual Analogue Scale (VAS),Lysholm Knee Scoring Scale,and Kellgren-Lawrence (K-L) Grading Scale,respectively. The TCM pattern was identified and quantified using a TCM Pattern Scoring Scale. Immunohistochemistry was used to determine the phosphorylation characteristics of Smad3 in articular cartilage,and ELISA was used to measure the contents of MMP-13 and TGF-β1 in synovial fluid. The level characteristics and their correlation with the degree of syndrome were analyzed.Results (i) There was no statistically significant difference in VAS scores,Lysholm scores,and K-L grades between KOA patients with different TCM patterns. (ii) Compared with KOA patients with pattern of intermingled phlegm and blood stasis,patients with pattern of liver-kidney deficiency had higher levels of MMP-13 in synovial fluid and lower levels of TGF-β1 in synovial fluid (P<0.05). (iii) In KOA patients with liver-kidney deficiency pattern,there was a positive correlation between the level of MMP-13 in synovial fluid and the score of TCM pattern (r=0.292,P=0.020),while there was a negative correlation between the level of TGF-β1 in synovial fluid and the score of TCM pattern (r=-0.781,P<0.001). In KOA patients with pattern of intermingled phlegm and blood stasis,there was also a positive correlation between the level of MMP-13 in synovial fluid and the score of TCM pattern (r=0.936,P<0.001). (iv) The mean optical density value of P-Smad3 in articular cartilage was lower in KOA patients with liver-kidney deficiency pattern than in pattern of intermingled phlegm and blood stasis (P<0.05).Conclusion KOA patients with liver-kidney deficiency pattern or pattern of intermingled phlegm and blood stasis have different levels of TGF-β1 and MMP-13 in synovial fluid,as well as varying degrees of Smad3 phosphorylation in articular cartilage,which is consistent with the analysis of etiology and pathogenesis under different patterns. The levels of TGF-β1 and MMP-13 in synovial fluid of patients with liver-kidney deficiency pattern can reflect the severity of the pattern to a certain extent,and the mechanism may be related to the inhibition of the activation level of the TGF-β/Smad signaling pathway. This study enriches the research content of the material basis of TCM patterns.

关键词

膝骨关节炎/肝肾亏虚证/痰瘀互结证/转化生长因子-β1/基质金属蛋白酶-13/Smad磷酸化

Key words

knee osteoarthritis/liver-kidney deficiency pattern/pattern of intermingled phlegm and blood stasis/transforming growth factor-β1/matrix metalloproteinase-13/phosphorylation of Smad3

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基金项目

国家自然科学基金青年科学基金项目(82104710)

北京中医药大学东直门医院青年后备人才项目(DZMG-QNHB0002)

出版年

2024
北京中医药大学学报
北京中医药大学

北京中医药大学学报

CSTPCD北大核心
影响因子：1.568
ISSN：1006-2157
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