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

doi:10.12092/j.issn.1009-2501.2018.07.004

中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (7): 743-748.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

黄立佳²，黄杨¹，孔劲松¹，郑鑫¹，宫小康¹，阮建伟¹，王海宝¹

¹台州市立医院，骨科，台州 318000，浙江；²浙江中医药大学，第二临床医学院，杭州 310053，浙江

收稿日期:2018-02-05 修回日期:2018-03-22 出版日期:2018-07-26 发布日期:2018-07-20
通讯作者: 王海宝，男，本科，主任医师，研究方向：骨关节疾病。 Tel：0576-88199590 E-mail：veasel_yang@163.com
作者简介:黄立佳，男，硕士研究生，研究方向：骨外科疾病。 Tel：15990010281 E-mail：1914516254@qq.com
基金资助:
浙江省中医药科技计划项目（2016ZA204）；浙江省公益技术应用研究项目（2017C37109）；浙江省实验动物科技计划项目（2018C37107）；台州市科技计划项目（1701KY44）

Inhibition of articular cartilage degeneration by atorvastatin calcium via STAT1-caspase-3 signaling axis in rats with knee osteoarthritis

HUANG Lijia², HUANG Yang¹, KONG Jinsong¹, ZHENG Xin¹, GONG Xiaokang¹, RUAN Jianwei¹, WANG Haibao¹

¹Department of Orthopedics, Taizhou Municipal Hospital, Taizhou 318000, Zhejiang, China; ²The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China

Received:2018-02-05 Revised:2018-03-22 Online:2018-07-26 Published:2018-07-20

摘要/Abstract

摘要：

目的: 探讨阿托伐他汀钙在膝骨关节炎（KOA）大鼠体内通过调节信号转导和转录激活因子1（STAT1）、半胱氨酸蛋白酶-3（caspase-3）的表达，从而对关节软骨退变的影响。方法: 将SD大鼠随机分为正常对照组、模型组、阿托伐他汀钙治疗组，采用Hulth法建立KOA大鼠模型，实验8周后采用酶联免疫吸附测定（ELISA）法检测大鼠血清中TNF-α及IL-1β的表达水平，膝关节X线影像学检查，关节软骨HE染色行病理学观察，检测软骨组织内p-STAT1和cleaved caspase-3蛋白表达水平。结果: 模型组大鼠血清中TNF-α及IL-1β含量明显高于正常组（P<0.01），而阿托伐他汀钙治疗组低于模型组（P<0.01）。阿托伐他汀钙治疗组X线表现与模型组相比，膝关节关节间隙、关节软骨破坏和骨赘形成等均有改善。阿托伐他汀钙能明显减轻膝关节病理变化，与模型组相比，阿托伐他汀钙治疗组关节软骨Mankin's评分显著降低（P<0.01）。模型组大鼠关节软骨p-STAT1和cleaved caspase-3蛋白表达水平明显高于正常组（P<0.01），而阿托伐他汀钙治疗组低于模型组（P<0.01），且相关分析表明，p-STAT1和cleaved caspase-3之间呈直线正相关（r=0.986, P<0.01）。结论: 阿托伐他汀钙经STAT1-caspase-3信号轴抑制膝关节炎症反应，从而改善KOA关节软骨的退变。

关键词: 膝骨关节炎, 阿托伐他汀钙, STAT1-caspase-3信号轴, 炎症因子

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 ELISA, 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.

Key words: knee osteoarthritis, atorvastatin calcium, STAT1-caspase-3 signaling axis, inflammatory cytokines

中图分类号:

R965.2

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, 23(7): 743-748.

HUANG Lijia, HUANG Yang, KONG Jinsong, ZHENG Xin, GONG Xiaokang, RUAN Jianwei, WANG Haibao. Inhibition of articular cartilage degeneration by atorvastatin calcium via STAT1-caspase-3 signaling axis in rats with knee osteoarthritis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(7): 743-748.

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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

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