舒筋活血胶囊通过JAK2/STAT3通路缓解大鼠膝骨关节炎的机制研究  

Mechanism of Shujin Huoxue Capsule in relieving knee osteoarthritis in rats through JAK2/STAT3 pathway

作　　者：李宏军[1] 钱亮 邓新超 余庭 吴岩 吴红丽 LI Hongjun;QIAN Liang;DENG Xinchao;YU Ting;WU Yan;WU Hongli(Department of Wound Repair and Peripheral Vascular Disease,the First Hospital of Wuhan,Wuhan 430030,China;Department of Orthopedics,the Eighth Hospital of Wuhan)

机构地区：[1]武汉市第一医院创面修复与周围血管病科,430030 [2]武汉市第八医院骨科

出　　处：《天津医药》2023年第9期961-967,共7页Tianjin Medical Journal

基　　金：武汉市卫生和计划生育委员会科研项目(WZ17Q11)。

摘　　要：目的探讨舒筋活血胶囊调控酪氨酸蛋白激酶2(JAK2)/信号转导及转录激活蛋白3(STAT3)信号通路对大鼠膝骨关节炎(KOA)的影响及其机制。方法采用Hulth法制备大鼠KOA模型,将60只大鼠分为假手术组(Sham组)、KOA组、舒筋活血胶囊组(SJHX组)(472.5 mg/kg舒筋活血胶囊灌胃)、AG490组(5.0 mg/kg的JAK2抑制剂AG490腹腔注射),每组15只。HE染色与番红O-固绿染色观察滑膜组织与软骨组织病理变化,酶联免疫吸附试验(ELISA)检测血清白细胞介素(IL)-10、IL-1β、肿瘤坏死因子α(TNF-α)水平,免疫荧光法检测M1/M2型巨噬细胞极化,免疫组化染色检测IL-1β、诱导型一氧化氮合成酶(iNOS)、基质金属蛋白酶(MMP)-13蛋白表达,Western blot检测JAK2/STAT3通路相关蛋白。结果与Sham组比较,KOA组大鼠关节面不平整,滑膜组织与软骨组织结构破坏,病理评分增加,血清IL-1β、TNF-α水平明显升高,IL-10水平降低,滑膜组织IL-1β、iNOS、MMP-13、p-JAK2/JAK2、p-STAT3/STAT3表达水平及M1、M2型巨噬细胞、M1/M2比值升高(P<0.05);与KOA组比较,SJHX组与AG490组大鼠滑膜组织与软骨组织病理损伤减轻,病理评分降低,血清IL-1β、TNF-α水平降低,IL-10水平升高,滑膜组织IL-1β、iNOS、MMP-13、p-JAK2/JAK2、p-STAT3/STAT3表达水平及M1巨噬细胞、M1/M2比值降低(P<0.05)。结论舒筋活血胶囊可通过抑制JAK2/STAT3信号通路激活,调节M1/M2巨噬细胞极化,改善KOA大鼠滑膜炎症状。Objective To investigate the effect and mechanism of Shujin Huoxue Capsule on knee osteoarthritis(KOA)in rats by regulating tyrosine protein kinase 2(JAK2)/signal transduction and transcription-activating protein 3(STAT3)signaling pathway.Methods The Hulth method was used to prepare rat KOA model.Sixty rats were divided into the Sham group,the KOA group,the Shujin Huoxue Capsule(SJHX)group(472.5 mg/kg Shujin Huoxue Capsule gavage)and the AG490 group(5.0 mg/kg JAK2 inhibitor AG490 intraperitoneally)with 15 rats in each group.The pathological changes of synovial tissue and cartilage tissue were observed by HE staining and Safranin O-fast green staining.Serum levels of interleukin-10(IL-10),IL-1b and tumor necrosis factor-a(TNF-a)were detected by enzyme-linked immunosorbent assay(ELISA).M1/M2 macrophage polarization was detected by immunofluorescence assay.The expression levels of IL-1β,inducible nitric oxide synthase(iNOS)and matrix metalloproteinase 13(MMP-13)were detected by immunohistochemical staining.JAK2/STAT3 pathway related proteins were detected by Western blot assay.Results Compared with the Sham group,the articular surface was uneven in rats of the KOA group.The synovial tissue and cartilage tissue were destroyed,pathological scores were increased.Serum levels of IL-1βand TNF-αwere obviously increased,and the level of IL-10 was obviously reduced.Expression levels of IL-1β,iNOS,MMP-13,p-JAK2/JAK2 and p-STAT3/STAT3 in synovial tissue,and the proportions of M1,M2 macrophages and M1/M2 were obviously increased(P<0.05).Compared with the KOA group,the pathological damage of synovial tissue and cartilage tissue was reduced in the SJHX group and the AG490 group.Pathological scores were reduced.Serum levels of IL-1βand TNF-αwere obviously reduced,and the level of IL-10 was obviously increased.Expression levels of IL-1β,iNOS,MMP-13,p-JAK2/JAK2,p-STAT3/STAT3 in synovial tissue,and the proportions of M1,M2 macrophages and M1/M2 were obviously reduced(P<0.05).Conclusion Shujin Huoxue Capsule can improve the sy

关 键 词：骨关节炎 膝 活血舒筋 巨噬细胞 JANUS激酶2 STAT3转录因子 舒筋活血胶囊 

分 类 号：R684.3[医药卫生—骨科学]