紫云英苷对膝关节骨性关节炎大鼠JNK/p38 MAPK信号通路的影响  

Effect of Astragalus Glycosides on JNK/p38 MAPK signaling pathway in rats with knee osteoarthritis

作　　者：杨博辰[1] 付学敬 朱琳[1] YANG Bochen;FU Xuejing;ZHU Lin(Department of orthopedics and traumatology,the Third Affiliated Hospital of Henan University of traditional Chinese medicine,Zhengzhou 450000,China)

机构地区：[1]河南中医药大学第三附属医院骨伤科,河南郑州450000

出　　处：《中国骨质疏松杂志》2022年第10期1491-1495,1500,共6页Chinese Journal of Osteoporosis

基　　金：郑州市科技攻关计划(20150143)。

摘　　要：目的探究紫云英苷对膝关节骨性关节炎(KOA)大鼠的保护作用以及对JNK/p38 MAPK信号通路的影响。方法90只SD大鼠随机分为假手术组、模型组、塞来昔布组(18 mg/kg)、紫云英苷低(25 mg/kg)、中(50 mg/kg)、高(100 mg/kg)剂量组,每组15只。改良Huith法建立KOA模型,术后灌胃6周。游标卡尺测量大鼠膝关节直径,足趾容积仪测量大鼠足趾容积;ELISA法检测血清IL-1β、IL-6、TNF-α水平;HE染色观察膝关节软骨组织病理变化;ELISA法检测软骨组织TGF-β1、MMP-3水平;Western Blot法检测p-JNK、JNK、p-p38 MAPK、p38 MAPK蛋白表达。结果与假手术组比较,模型组大鼠软骨组织表面被破坏,组织层变薄,细胞数量减少且排列紊乱,潮线被大量破坏;膝关节直径与足趾容积明显变大(P<0.05);血清中IL-1β、IL-6、TNF-α水平以及软骨组织中TGF-β1、MMP-3水平,p-JNK/JNK、p-38 MAPK/p38 MAPK比值显著升高(P<0.05)。与模型组比较,塞来昔布组与紫云英苷各剂量组软骨组织病变明显减轻;膝关节直径与足趾容积明显缩小(P<0.05);血清中IL-1β、IL-6、TNF-α水平以及软骨组织中TGF-β1、MMP-3水平,p-JNK/JNK、p-38 MAPK/p38 MAPK比值显著降低(P<0.05),且紫云英苷各剂量组间具有剂量效应(P<0.05);紫云英苷高剂量组与塞来昔布组比较差异无统计学意义(P>0.05)。结论紫云英苷可能通过抑制JNK/p38 MAPK信号通路激活,减轻炎症反应,改善KOA大鼠膝关节软骨组织损伤。Objective To explore the protective effect of astragalus glycosides on knee osteoarthritis(KOA)rats and it impact on JNK/p38 MAPK signaling pathway.Methods Ninety SD rats were separated into sham operation group,model group,celecoxib group(18 mg/kg),astragalus low(25 mg/kg),medium(50 mg/kg),high(100 mg/kg)dose groups randomly,15 per group.The modified Huith method was performed to establish the KOA model,Postoperative gavage lasted for 6 weeks.The diameter of the rat’s knee joint was measured with a vernier caliper,and the toe volume of the rat was measured with a toe volume meter;serum LEVELS of IL-1β,IL-6 and TNF-αwere determined by ELISA;HE staining was used to observe the pathological changes of knee cartilage.The contents of TGF-β1 and MMP-3 in cartilage tissue were detected by ELISA.The protein expressions of P-JNK,JNK,P-P38 MAPK and p38 MAPK were detected by Western Blot.Results Compared with the sham operation group,the surface of the cartilage tissue in the model group was destroyed,the tissue layer became thinner,the number of cells was reduced and the arrangement was disordered,and the tide line was largely destroyed;the diameter of the knee joint and the volume of the toes increased obviously(P<0.05);the serum IL-1β,IL-6,TNF-αcontents and cartilage tissue TGF-β1,MMP-3 contents,p-JNK/JNK,p-38 MAPK/p38 MAPK ratio increased obviously(P<0.05).Compared with the model group,the cartilage tissue lesions of the celecoxib group and the astragalus glycoside groups were obviously reduced;the diameter of the knee joint and the volume of the toes reduced obviously(P<0.05);the serum IL-1β,IL-6,TNF-αcontents and cartilage tissue TGF-β1,MMP-3 contents,p-JNK/JNK,p-38 MAPK/p38 MAPK ratio reduced obviously(P<0.05),and there was a dose effect among the different dose Astragalus glycosides groups(P<0.05);There was no significant difference in the above indicators between the high-dose Astragalus glycoside group and the celecoxib group(P>0.05).Conclusion Astragalus glycosides may inhibit the activation of the JN

关 键 词：紫云英苷 膝关节骨性关节炎 c-Jun-N末端激酶 P38丝裂原活化蛋白激酶 

分 类 号：R285.5[医药卫生—中药学]