Anti-Inflammatory Effects of Hydrophilic and Lipophilic Statins with Hyaluronic Acid Against LPS-Induced Inflammation in Porcine Articular Chondrocytes
Anti-Inflammatory Effects of Hydrophilic and Lipophilic Statins with Hyaluronic Acid Against LPS-Induced Inflammation in Porcine Articular Chondrocytes
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DOI：
10.1002/jor.22536
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发表时间：
2014-04-01
影响因子：
2.8
通讯作者：
Savitha, Sivasubramanian
中科院分区：
文献类型：
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作者：
Chang, Chih-Hung;Hsu, Yuan-Ming;Savitha, Sivasubramanian
本研究的目的是通过体外LPS诱导的关节软骨细胞炎症模型，了解亲脂性（辛伐他汀）和亲水性他汀类药物（普伐他汀）联合/不联合透明质酸治疗骨关节炎的疗效。HA与不同剂量的辛伐他汀或普伐他汀联合使用。除细胞毒性外，还分析了他汀类药物对NO产生、促炎细胞因子、炎性介质和NF-B p50蛋白的影响。TUNEL法检测DNA链断裂。两种他汀类药物在不加HA的情况下沿着给药时，降低NF-B活性的能力较低。基因表达表明，辛伐他汀和普伐他汀有能力降低促炎和炎症介质水平。高剂量辛伐他汀联合或不联合HA均下调炎性细胞因子，但导致更高的细胞毒性。TUNEL法证实了他汀类药物与HA或不与HA对软骨细胞凋亡的调节作用，尤其是在亲水性他汀类药物中。炎症介质的显著下调表明，关节内注射HA联合他汀类药物可能可行地减缓骨关节炎的进展。辛伐他汀或普伐他汀与透明质酸联合应用可能对OA治疗产生有益的效果，但当使用亲水性他汀时效果更好。(c)2013骨科研究学会。由威利期刊公司出版J Orthop Res 32：557-565，2014.
The objective of the study is to understand the therapeutic effects of lipophilic (simvastatin) and hydrophilic statins (pravastatin) combined with/without hyaluronic acid for osteoarthritis by an in vitro LPS-induced inflammatory model of articular chondrocytes. HA in combination with different doses of simvastatin or pravastatin were used. Beside cytotoxicity, the influence of statins on NO production, pro-inflammatory cytokine, inflammatory mediators, and NF-B p50 protein were analyzed. Finally, TUNEL assay was performed to detect DNA strand breakage. Two statins were less able to lower NF-B activity when they were administrated along without HA. The gene expression demonstrates that simvastatin and pravastatin had the ability to decrease pro-inflammatory and inflammatory mediator levels. High dose simvastatin with or without HA down regulated inflammatory cytokines, but resulted in higher cytotoxicity. TUNEL assay confirms the regulatory effect of statins with or without HA over the apoptosis of chondrocytes, especially in hydrophilic statins. The significant down-regulation of inflammatory mediators suggests that intra-articular injection of HA in combination with statins might feasibly slow the progress of osteoarthritis. Administration of simvastatin or pravastatin with hyaluronic acid may produce beneficial effects for OA treatment, but with better results when hydrophilic statin was used. (c) 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:557-565, 2014.