中国临床药理学与治疗学Issue(7)：743-748,6.DOI:10.12092/j.issn.1009-2501.2018.07.004
阿托伐他汀钙经STAT1-caspase-3信号轴抑制膝骨关节炎大鼠关节软骨退变的研究
Inhibition of articular cartilage degeneration by atorvastatin calcium via STAT1-caspase-3 signaling axis in rats with knee osteoarthritis
摘要
Abstract
AIM:To investigate the effect of atorvastatin calcium on the expression of STAT1, caspase-3 and on degeneration of articular cartilage in the knee osteoarthritis (KOA) rats.METHODS:SD rats were randomly divided into normal control group, model group and atorvastatin calcium treatment group.KOA rat model was established by Hulth method.After 8 weeks of experiment, the expression of TNF-α and IL-1β in serum of rats were detected by ELASA, X-ray examination was used to detect knee joint, articular cartilage HE staining were used for pathological observation, cartilage tissue p-STAT1 and cleaved caspase-3 protein expression levels were observed by immunohistochemistry and western blot.RESULTS:The levels of serum TNF-α and IL-1β in model group were significantly higher than those in normal group (P ＜ 0.01), while those in atorvastatin calcium group were lower than those in model group (P ＜ 0.01).Compared with the model group, the X-ray findings of atorvastatin calcium treatment group showed improvement of knee joint space, articular cartilage destruction and osteophyte formation.Atorvastatin calcium could significantly reduce the pathological changes of knee joint.Compared with model group, Mankin 's score of articular cartilage in atorvastatin calcium treatment group decreased significantly (P ＜ 0.01).The expression of p-STAT1 and cleaved caspase-3 protein in articular cartilage of model group was significantly higher than that of normal group (P ＜ 0.01), while that of atorvastatin calcium group was lower than that of model group (P ＜ 0.01), and the correlation analysis showed that there was a linear positive correlation between p-STAT1 and cleaved caspase-3 (r =0.986, P ＜ 0.01).CONCLUSION:Atorvastatin inhibits the inflammation of the knee joint via STAT1-caspase-3 signal axis, thereby improving the degeneration of KOA articular cartilage.关键词
膝骨关节炎/阿托伐他汀钙/STAT1-caspase-3信号轴/炎症因子Key words
knee osteoarthritis/atorvastatin calcium/STAT1-caspase-3 signaling axis/inflammatory cytokines分类
医药卫生引用本文复制引用
黄立佳,黄杨,孔劲松,郑鑫,宫小康,阮建伟,王海宝..阿托伐他汀钙经STAT1-caspase-3信号轴抑制膝骨关节炎大鼠关节软骨退变的研究[J].中国临床药理学与治疗学,2018,(7):743-748,6.基金项目
浙江省中医药科技计划项目(2016ZA204) （2016ZA204）
浙江省公益技术应用研究项目(2017C37109) （2017C37109）
浙江省实验动物科技计划项目(2018C37107) （2018C37107）
台州市科技计划项目(1701KY44) （1701KY44）
