摘要
Abstract
Objective To investigate therapeutic effects of pristimerin(PM)on post-traumatic osteoarthritis(PTOA)rats by regulating the Yes-associated protein(YAP)/transcriptional co-activator with 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 inhibitor VTPF 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),tumor necrosis 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)as-say was used to detect mRNA of TAZ,IL-1β and TNF-α in rat cartilage tissue.Western Blot was applied to detect YAP/TAZ sig-naling 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-α and their mRNA,NO,MMP-1,MMP3,apoptosis rate,and Mankin's score in cartilage tissue were obviously higher(P<0.05).HE showed that the cartilage layer became thinner,the structure was unclear,and a large number of 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 inhibitor VTPF 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 pathway.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Key words
pristimerin/Yes-associated protein/transcriptional co-activator with a PDZ-binding domain signaling path-way/post-traumatic osteoarthritis/treatment分类
医药卫生
