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阿托伐他汀(一种HMG-CoA还原酶抑制剂)对碘乙酸钠诱导的骨关节炎疼痛的影响:对骨关节炎治疗的意义

Effect of atorvastatin, a HMG-CoA reductase inhibitor in monosodium iodoacetate-induced osteoarthritic pain: implication for osteoarthritis therapy.

作者信息

Pathak Nitya N, Balaganur Venkanna, Lingaraju Madhu C, Kant Vinay, Kumar Dhirendra, Kumar Dinesh, Sharma Anil K, Tandan Surendra K

机构信息

Division of Pharmacology and Toxicology, Bareilly, India.

Division of Pathology, Indian Veterinary Research Institute, Bareilly, India.

出版信息

Pharmacol Rep. 2015 Jun;67(3):513-9. doi: 10.1016/j.pharep.2014.12.005. Epub 2014 Dec 19.

Abstract

BACKGROUND

Oxidative stress is one of the main causes of pain and cartilage degradation in osteoarthritis. This study on atorvastatin, a HMG-CoA reductase inhibitor used in the treatment of hypercholesterolemia and prevention of coronary heart disease aimed to investigate its effect on hyperalgesia and cartilage damage in monosodium iodoacetate (MIA)-induced osteoarthritis model in rats.

METHODS

Osteoarthritis was induced by a single intra-articular injection of 3mg MIA. After daily administration of atorvastatin (3, 10 and 30 mg/kg) for 20 days by oral gavage, pain was assessed on days 0, 1, 3, 7, 14 and 21. Histopathology of ipsilateral knee joint; oxidative markers and antioxidants in plasma were assessed on day 21.

RESULTS

Atorvastatin attenuated hyperalgesia. The increased level of lipid peroxidation, superoxide, protein carbonyl; decreased activity of catalase, glutathione-S-transferase, reduced glutathione and total thiol levels in MIA rats were restored to the normal levels, however, superoxide dismutase and nitric oxide levels remained unaltered by atorvastatin. Further, atorvastatin reduced the MIA-induced histopathological alteration in the knee joint.

CONCLUSION

Our study demonstrated that atorvastatin attenuates MIA-induced osteoarthritic pain and protect cartilage degradation through inhibition of oxidative stress suggesting its importance in osteoarthritic pain management.

摘要

背景

氧化应激是骨关节炎中疼痛和软骨降解的主要原因之一。本研究针对用于治疗高胆固醇血症和预防冠心病的HMG-CoA还原酶抑制剂阿托伐他汀,旨在研究其对碘乙酸钠(MIA)诱导的大鼠骨关节炎模型中痛觉过敏和软骨损伤的影响。

方法

通过关节腔内单次注射3mg MIA诱导骨关节炎。通过口服灌胃每日给予阿托伐他汀(3、10和30mg/kg),持续20天,在第0、1、3、7、14和21天评估疼痛情况。在第21天评估同侧膝关节的组织病理学;评估血浆中的氧化标志物和抗氧化剂。

结果

阿托伐他汀减轻了痛觉过敏。MIA大鼠中脂质过氧化、超氧化物、蛋白质羰基水平升高;过氧化氢酶、谷胱甘肽-S-转移酶活性降低,还原型谷胱甘肽和总硫醇水平降低,这些指标均恢复到正常水平,然而,阿托伐他汀对超氧化物歧化酶和一氧化氮水平没有影响。此外,阿托伐他汀减轻了MIA诱导的膝关节组织病理学改变。

结论

我们的研究表明,阿托伐他汀可减轻MIA诱导的骨关节炎疼痛,并通过抑制氧化应激保护软骨降解,表明其在骨关节炎疼痛管理中的重要性。

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