基于SDF-1/CXCR4途径的骨炎消方体外干预对兔膝骨关节炎软骨组织的保护机制研究  

Study on the Protective Mechanism of Guyanxiao Recipe on the Osteoarthritis in Cartilage Tissue of Rabbit Knee Based on SDF-1/CXCR4 Pathway

作　　者：张琪 王琳 李田洋 王宝娟 郑曙光 Zhang Qi;Wang Lin;Li Tianyang;Wang Baojuan;Zheng Shuguang(Guizhou University of Traditional Chinese Medicine,Guiyang 550025;The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550001)

机构地区：[1]贵州中医药大学,贵阳550025 [2]贵州中医药大学第一附属医院,贵阳550001

出　　处：《中药药理与临床》2021年第2期133-138,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金项目(编号:81660823,81960914)。

摘　　要：目的:研究骨炎消方体外干预对兔膝骨关节炎(KOA)软骨组织的保护作用。方法:采用生化检测法筛选骨炎消给药浓度,分为骨炎消方360 mg/mL、720 mg/mL、1440 mg/mL组及盐酸氨基葡萄糖10 mmol/L组,分别处理培养KOA家兔软骨组织,观察软骨形态学改变,评估关节软骨蛋白聚糖丢失程度;检测上清液及软骨组织中关于基质细胞衍生因子-1(SDF-1)/CXC趋化因子受体4(CXCR4)信号通路上相关细胞因子的表达水平。结果:与正常对照组比较,模型对照组培养上清液中CXCR4含量显著升高,COL-Ⅱ含量显著下降(P<0.01);软骨组织中CXCR4蛋白及mRNA、IL-1β mRNA、MMP-13蛋白表达显著上调(P<0.01)。与模型对照组比较,骨炎消方各浓度组均能够明显降低KOA模型培养上清液中CXCR4含量,提高COL-Ⅱ含量(P<0.05或P<0.01);能明显下调KOA软骨组织中CXCR4蛋白及mRNA、IL-1β mRNA、MMP-13蛋白表达水平(P<0.05或P<0.01);能够缓解KOA模型软骨组织番红失染,改善组织畸变的情况。结论:骨炎消方可以通过调节SDF-1/CXCR4信号通路,降低CXCR4水平、促进COL-Ⅱ及蛋白聚糖的合成,减少MMP-13及IL-1β的释放,从而改善KOA引起的软骨组织退化。Objective: To study the protective effect of Guyanxiao Recipe on cartilage tissue of rabbit knee with osteoarthritis(KOA) in vitro. Methods: Biochemical detection method was used to determine the administration concentration of Guyanxiao, and animals were divided into 360 mg/mL, 720 mg/mL, 1440 mg/mL Guyanxiao extract groups and 10 mmol/L glucosamine hydrochloride group. Rabbit cartilage tissues in KOA were treated and cultured, the changes of cartilage morphology were observed to evaluate the loss of articular cartilage proteoglycans. Then the expression levels of related cytokines in the SDF-1/CXCR4 signaling pathway in the supernatant and cartilage tissue were detected. Results: Compared with the control group, the CXCR4 content in the culture supernatant in the model group was significantly increased, and the COL-Ⅱ content was significantly decreased(P<0.01). The mRNA and protein expressions of CXCR4,the expressions of IL-1βmRNA and MMP-13 protein in cartilage tissues were significantly increased(P<0.01). Compared with the model group, the CXCR4 content in the culture supernatant of the KOA model was significantly reduced in all doses of Guyanxiao extract groups, the COL-Ⅱ content was increased(P<0.01), while the expression levels of mRNA and protein of CXCR4, IL-1βmRNA and MMP-13 protein in the KOA model tissues were significantly down-regulated(P<0.05 or P<0.01), the loss of safranin in the cartilage tissue of the KOA model was alleviated.Conclusion: Guyanxiao Recipe can reduce the level of CXCR4, promote the synthesis of COL-Ⅱ and proteoglycans, and reduce the release of MMP-13 and IL-1β by regulating the SDF-1/CXCR4 signaling pathway, in order to improve cartilage tissue degradation caused by KOA.

关 键 词：骨炎消方 膝骨关节炎 体外培养软骨组织 基质细胞衍生因子-1/CXC趋化因子受体4(SDF-1/CXCR4)信号通路 

分 类 号：R285.5[医药卫生—中药学]