扁蒴藤素调节YAP/TAZ信号通路对创伤性关节炎大鼠的治疗作用研究  

Study on Therapeutic Effects of Pristimerin on Post-Traumatic Osteoarthritis Rats by Regulating the YAP/TAZ Signaling Pathway

作　　者：余华[1] 李少星[1] 刘相杰 Yu Hua;Li Shaoxing;Liu Xiangjie(The First Affiliated Hospital of Chengdu Medical College,Chengdu,Sichuan 610500,China.)

机构地区：[1]成都医学院第一附属医院,四川成都610500

出　　处：《四川医学》2024年第5期491-496,共6页Sichuan Medical Journal

摘　　要：目的探究扁蒴藤素(PM)调节Yes相关蛋白(YAP)/转录共激活因子PDZ结合基序(TAZ)信号通路对创伤性关节炎(PTOA)大鼠的治疗作用。方法将SD雄性大鼠随机分为对照组、PTOA组、低剂量PM组(PM-L组,100 mg/kg PM)、高剂量PM组(PM-H组,200 mg/kg PM)和高剂量PM+YAP抑制剂VTPF组(PM-H+VTPF组,200 mg/kg PM+10 mg/kg VTPF),每组12只。记录大鼠热痛阈值、压痛阈值的变化。HE染色观察大鼠软骨组织病理学变化,并进行Mankin s评分,酶联免疫吸附试验(ELISA)检测大鼠软骨组织中炎症因子一氧化氮(NO)、白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和基质金属蛋白酶(MMP)-1、MMP-3水平。TUNEL染色观察大鼠软骨组织细胞凋亡的情况。实时荧光定量PCR(RT-qPCR)实验检测大鼠软骨组织TAZ、IL-1β、TNF-αmRNA水平。Western Blot检测大鼠软骨组织YAP/TAZ信号通路相关蛋白的表达情况。结果与对照组相比,PTOA组大鼠热痛阈值、压痛阈值、软骨组织YAP磷酸化水平、TAZ蛋白水平与mRNA水平显著降低(P<0.05),软骨组织IL-1β、TNF-α及其mRNA水平、NO、MMP-1、MMP3水平、细胞凋亡率、Mankin s评分显著升高(P<0.05),HE显示软骨层变薄,结构不清晰,软骨细胞大量丢失、排列紊乱。与PTOA组相比,PM-L组、PM-H组大鼠相关指标变化与上述相反(P<0.05),软骨组织病变减轻。YAP抑制剂VTPF减轻了PM对PTOA的治疗作用。结论PM可能通过激活YAP/TAZ信号通路,对PTOA大鼠具有一定的治疗作用。Objective To investigate therapeutic effects of pristimerin(PM)on post-traumatic osteoarthritis(PTOA)rats by regulating the Yes-associated protein(YAP)/transcriptional co-activatoRwith a PDZ-binding domain(TAZ)signaling pathway.Methods SD male rats were randomly separated into a control group,a PTOA group,a low-dose PM group(PM-L group,100 mg/kg PM),a high-dose PM group(PM-H group,200 mg/kg PM),and a high-dose PM+YAP inhibitoRVTPF group(PM-H+VTPF group,200 mg/kg PM+10 mg/kg VTPF),with 12 rats in each group.Changes in the thermal pain threshold and tenderness threshold of rats were recorded.HE staining was applied to observe pathological changes in rat cartilage tissue and Mankin s score was performed.Enzyme linked immunosorbent assay(ELISA)was applied to detect inflammatory factors such as nitric oxide(NO),interleukin-1β(IL-1β),tumoRnecrosis factor-α(TNF-α),matrix metalloproteinase-1(MMP-1),and MMP-3 in cartilage tissue.TUNEL staining was applied to observe apoptosis of cartilage tissue cells.Real time fluorescence quantitative PCR(RT-qPCR)assay was used to detect mRNA of TAZ,IL-1βand TNF-αin rat cartilage tissue.Western Blot was applied to detect YAP/TAZ signaling pathway related proteins in cartilage tissue.Results Compared with control group,thermal pain threshold,tenderness threshold,YAP phosphorylation in cartilage tissue,and TAZ protein and mRNA in the PTOA group were significantly lower(P<0.05)while IL-1β,TNF-αand theiRmRNA,NO,MMP-1,MMP3,apoptosis rate,and Mankin s score in cartilage tissue were obviously higher(P<0.05).HE showed that the cartilage layeRbecame thinner,the structure was unclear,and a large numbeRof chondrocytes were lost and arranged in disorder.Compared with PTOA group,changes in relevant indicators of rats in the PM-L and PM-H groups were opposite to the above(P<0.05),and the cartilage tissue lesions were reduced.YAP inhibitoRVTPF alleviated the therapeutic effect of PM on PTOA.Conclusion PM may have a certain therapeutic effect on PTOA rats by activating the YAP/TAZ signaling pat

关 键 词：扁蒴藤素 Yes相关蛋白/转录共激活因子PDZ结合基序信号通路 创伤性关节炎 治疗 

分 类 号：R-332[医药卫生]