骨碎补醇提物对骨关节炎大鼠滑膜组织中TLR4-NF-κB信号转导的影响  

The effect of Rhizoma Drynaria ethanol extract on knee osteoarthritis in rats via inhibiting TLR4-NF-κB signaling pathway

作　　者：许建[1] 刘天泽[1] 郑寿鹏[1] 王雷[2] XU Jian;LIU Tian-ze;ZHENG Shou-peng;WANG Lei(Department of Surgery,Midong Hospital,Urumqi 830021;Department of Orthopaedics,People′s Hospital of Xinjiang Uygur Autonomous Region,Urumqi 830001,China)

机构地区：[1]新疆维吾尔自治区人民医院米东医院外科,乌鲁木齐830001 [2]新疆维吾尔自治区人民医院骨科,乌鲁木齐830001

出　　处：《解剖科学进展》2023年第4期419-422,426,共5页Progress of Anatomical Sciences

基　　金：新疆维吾尔自治区自然科学基金(2018D01C046)。

摘　　要：目的探讨骨碎补醇提物(RDE)对膝关节骨性关节炎的作用及分子机制。方法将60只雄性SD大鼠分为假手术组、模型组、RDE(2 g/kg、4 g/kg、8 g/kg)组,共计5组;在第0天,采用右膝关节前交叉韧带切断术复制大鼠膝关节骨性关节炎(KOA)模型,手术前和术后分别测量大鼠的机械性痛阈值和膝关节直径,每周一次,第14天开始灌胃给药,连续3周,腹主动脉取血,脱颈椎处死,解剖分离大鼠膝关节滑膜组织;采用ELISA法检测大鼠血清中IL-6、IL-1β、TNF-α的分泌水平;采用RT-PCR法检测大鼠膝关节滑膜组织中IL-6、IL-1β、TNF-α的表达;采用Western blot法检测大鼠膝关节滑膜组织中TLR4-NF-κB信号相关分子的表达。结果与术前大鼠比较,术后模型组大鼠的机械性痛阈值显著减少,膝关节直径显著增加,RDE显著增加KOA大鼠的机械性痛阈值和减少膝关节直径。RDE显著抑制KOA大鼠血清和滑膜组织中IL-6、IL-1β、TNF-α的表达水平,抑制KOA大鼠膝关节滑膜组织的炎性细胞浸润和滑膜增生,抑制KOA大鼠滑膜组织中TLR4、Myd88、p-IκB、p-p65/p65的表达水平。结论RDE对膝关节骨性关节炎具有潜在的保护作用,与抑制TLR4-NF-κB通路活化相关。Objective To investigate the effect and related molecular mechanism of Rhizoma Drynaria ethanol extract(RDE)on knee osteoarthritis.Methods 60 male SD rats were divided into sham group,model group,RDE(2 g/kg,4 g/kg,8 g/kg,the 14th day intragastric administration for 3 weeks)groups.On the 0 th day,knee osteoarthritis(KOA)models were established with right knee anterior cruciate ligament severance,and the mechanical pain threshold and knee diameter were measured before and after surgery respectively,once a week.The levels of IL-6,IL-1βand TNF-αin serum were detected by ELISA.The expressions of IL-6,IL-1βand TNF-αin rat synovial tissue were detected by RT-PCR.The level of TLR4/NF-κB signal-related molecules in the synovial tissue of rat knee joint was detected by Western blot.Results Compared with the sham operation group,the mechanical pain threshold was significantly reduced,and the knee joint diameter was significantly increased in model group.RDE(2 g/kg,4 g/kg,8 g/kg)significantly increased the mechanical pain threshold and reduced knee diameter in a dose⁃and time⁃dependent manner,down⁃regulated the secretion levels of IL-6,IL-1βand TNF-αin the serum and synovial tissue,inhibited inflammatory cells infiltration and synovial hyperplasia,down⁃regulated the levels of TLR4,Myd88,p-IκB and p-p65/p65 in the synovial tissue in KOA rat.Conclusion The potential protective effect of RDE on knee osteoarthritis is related to the inhibition of TLR4-NF-κB pathway activation in KOA rat.

关 键 词：骨碎补醇提物 膝关节骨性关节炎 核因子-ΚB 炎症 SD大鼠 

分 类 号：R684.3[医药卫生—骨科学]