瑞香素调节MCP-1/CCR2通路对骨关节炎大鼠软骨细胞焦亡的影响  

Effect of daphnetin on pyroptosis of chondrocytes in osteoarthritis rats by regulating the MCP-1/CCR2 pathway

作　　者：汤洁 李烨 胡勇 赵胜豪 李子熙 黄辉 TANG Jie;LI Ye;HU Yong;ZHAO Shenghao;LI Zixi;HUANGF Hui(Department of Osteoarthrosis,Gutian Hospital,the Fourth Hospital of Wuhan,Wuhan 430035,China)

机构地区：[1]武汉市第四医院古田院区骨关节科,湖北武汉430035

出　　处：《中国骨质疏松杂志》2024年第12期1731-1736,共6页Chinese Journal of Osteoporosis

基　　金：武汉市医学科研项目资助(WX21Q63)。

摘　　要：目的 探讨瑞香素(DAPH)调节MCP-1/CCR2信号轴对骨关节炎(OA)大鼠软骨细胞焦亡的影响。方法 通过切除前交叉韧带、内侧半月板建立OA大鼠模型,并随机分为OA组、DAPH低剂量(DAPH-L,30 mg/kg)组、DAPH高剂量(DAPH-H,90 mg/k)组、DAPH-H+CCL2(5 ng CCL2)组以及塞来昔布(20 mg/kg)组,并以仅打开关节腔的10只大鼠为假手术组,影像学分析骨密度值(BMD)、骨小梁数(Tb-N)以及骨体积分数(BV/TV);ELISA检测各组血清中白细胞介素(IL)-1β和IL-18水平;HE、番红检测软骨组织形态学变化;qRT-PCR检测软骨组织焦亡相关(ASC、NLRP3、Caspase-1)的基因表达;Western blot检测软骨组织MCP-1、CCR2蛋白表达。结果 与假手术组相比,OA组BMD、Tb-N、BV/TV降低,血清中IL-1β和IL-18水平、软骨组织ASC、NLRP3、Caspase-1 mRNA、MCP-1、CCR2蛋白表达增加(P<0.05);与OA组相比,DAPH-L组、DAPH-H组、塞来昔布组BMD、Tb-N、BV/TV增加,血清中IL-1β和IL-18水平、软骨组织ASC、NLRP3、Caspase-1 mRNA、MCP-1、CCR2蛋白表达降低,且DAPH-L组分别与DAPH-H组、塞来昔布组差异有统计学意义(P<0.05),但DAPH-H组、塞来昔布组间差异无统计学意义(P>0.05);与DAPH-H组相比,DAPH-H+CCL2组BMD、Tb-N、BV/TV降低,血清中IL-1β和IL-18水平、软骨组织ASC、NLRP3、Caspase-1 mRNA、MCP-1、CCR2蛋白表达增加(P<0.05)。结论 DAPH通过调节MCP-1/CCR2信号轴减少OA大鼠软骨细胞焦亡。Objective To investigate the effect of daphnetin(DAPH)on pyroptosis of chondrocytes in osteoarthritis(OA)rats by regulating the MCP-1/CCR2 signaling axis.Methods A rat model of osteoarthritis was established by removing the anterior cruciate ligament and medial meniscus,and was randomly separated into an OA group,a low-dose DAPH(DAPH-L,30 mg/kg)group,a high-dose DAPH(DAPH-H,90 mg/k)group,a DAPH-H+CCL2(5 ng CCL2)group,and a celecoxib(20 mg/kg)group.Ten rats with only open joint cavities were used as the sham surgery group,imaging was applied to analyze bone density(BMD),trabecular bone number(Tb-N),and bone volume fraction(BV/TV);ELISA was applied to detect the levels of interleukin-1β(IL-1β)and IL-18 in the serum of each group;HE and safranin were applied to detect morphological changes in cartilage tissue;qRT-PCR was applied to detect gene expression related to cartilage tissue necrosis(ASC,NLRP3,Caspase-1);Western blot was applied to detect the expression of MCP-1 and CCR2 proteins in cartilage tissue.Results Compared with the sham surgery group,the BMD,Tb-N,BV/TV in the OA group were decreased,the levels of IL-1βand IL-18 in serum,and the expression of ASC,NLRP3,Caspase-1 mRNA,MCP-1,and CCR2 proteins in cartilage tissue were increased(P<0.05);compared with the OA group,the BMD,Tb-N,BV/TV in the DAPH-L group,DAPH-H group,and celecoxib group were increased,the levels of IL-1βand IL-18 in serum,and the expression of ASC,NLRP3,Caspase-1 mRNA,MCP-1,and CCR2 proteins in cartilage tissue were reduced,and there was a statistically obvious difference between the DAPH-L group with the DAPH-H group and the celecoxib group,respectively(P<0.05),but there was no statistically obvious difference between the DAPH-H group and the celecoxib group(P>0.05);compared with the DAPH-H group,the BMD,Tb-N,BV/TV in the DAPH-H+CCL2 group were decreased,the levels of IL-1βand IL-18 in serum,and the expression of ASC,NLRP3,Caspase-1 mRNA,MCP-1,and CCR2 proteins in cartilage tissue were increased(P<0.05).Conclusion DAPH reduces pyropto

关 键 词：瑞香素 MCP-1/CCR2信号轴 骨关节炎 细胞焦亡 

分 类 号：R285.5[医药卫生—中药学]