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醋酸甲基泼尼松龙和曲安奈德剂量滴定对白细胞介素-1预处理的马关节软骨外植体的体外影响。

Effects of dosage titration of methylprednisolone acetate and triamcinolone acetonide on interleukin-1-conditioned equine articular cartilage explants in vitro.

作者信息

Dechant J E, Baxter G M, Frisbie D D, Trotter G W, McIlwraith C W

机构信息

Equine Orthopaedic Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA.

出版信息

Equine Vet J. 2003 Jul;35(5):444-50. doi: 10.2746/042516403775600479.

DOI:10.2746/042516403775600479
PMID:12875321
Abstract

REASONS FOR PERFORMING STUDY

Osteoarthritis is a frequent sequela of joint disease, especially with severe injuries or if attempts at therapy are unsuccessful. Negative and positive effects of corticosteroid treatment of articular cartilage have been demonstrated by in vitro and in vivo studies.

OBJECTIVES

To assess the metabolic effects of varying dosages of methylprednisolone acetate (MPA) and triamcinolone acetonide (TA) on interleukin-1alpha (IL-1) conditioned equine cartilage explants. Our hypothesis was that lower dosages of corticosteroids would be less detrimental to cartilage metabolism than higher dosages. TA would be less detrimental to cartilage metabolism than MPA.

METHODS

Treatment groups included articular cartilage explants with no IL-1 (control), IL-1 alone, and IL-1 plus 10, 5, 1 and 0.5 mg/ml MPA or 1.2, 0.6, 0.12 and 0.06 mg/ml TA. Explants were labelled with 35SO4 prior to the beginning and end of the experiment to assess glycosaminoglycan (GAG) degradation and synthesis, respectively. Total GAG content in media and explants and total cartilage DNA were also analysed.

RESULTS

MPA and TA reduced GAG synthesis compared to control and IL-1 alone. The highest dosage of MPA (10 mg/ml) reduced GAG synthesis less than lower dosages of MPA and all dosages of TA. Compared to IL-1 alone, all dosages of TA and lower dosages of MPA increased GAG degradation. MPA at 10 mg/ml reduced GAG degradation. Both MPA and TA increased media GAG content compared to control and IL-1 explants. Total cartilage GAGs were unchanged with MPA, but reduced with TA, compared with IL-1 alone. Total cartilage DNA was decreased with MPA and increased with TA compared to IL-1 and control explants.

CONCLUSIONS

MPA and TA did not counteract the negative effects of IL-1 and did not maintain cartilage metabolism at control levels. Lower dosages of MPA and TA were not less detrimental to cartilage metabolism than higher dosages. TA did not appear to be less harmful than MPA on cartilage metabolism. The results of this study differ from the findings of comparable in vivo studies.

POTENTIAL RELEVANCE

The low numbers of horses used in this study limits extrapolation of these findings to the equine population; however, this study also questions the clinical relevance of this in vitro model.

摘要

开展本研究的原因

骨关节炎是关节疾病常见的后遗症,尤其是在严重损伤或治疗尝试未成功的情况下。体外和体内研究已证实皮质类固醇治疗关节软骨的正负效应。

目的

评估不同剂量的醋酸甲泼尼龙(MPA)和曲安奈德(TA)对白细胞介素 - 1α(IL - 1)作用下的马软骨外植体的代谢影响。我们的假设是,较低剂量的皮质类固醇对软骨代谢的损害小于较高剂量。TA对软骨代谢的损害小于MPA。

方法

治疗组包括未加IL - 1的关节软骨外植体(对照)、单独使用IL - 1以及IL - 1加10、5、1和0.5mg/ml MPA或1.2、0.6、0.12和0.06mg/ml TA。在实验开始和结束前用35SO4标记外植体,分别评估糖胺聚糖(GAG)的降解和合成。还分析了培养基和外植体中的总GAG含量以及总软骨DNA。

结果

与对照和单独使用IL - 1相比,MPA和TA降低了GAG合成。MPA的最高剂量(10mg/ml)比MPA的较低剂量和所有剂量的TA对GAG合成的降低作用更小。与单独使用IL - 1相比,所有剂量的TA和MPA的较低剂量增加了GAG降解。10mg/ml的MPA降低了GAG降解。与对照和IL - 1外植体相比,MPA和TA均增加了培养基中的GAG含量。与单独使用IL - 1相比,MPA处理后总软骨GAGs不变,但TA处理后降低。与IL - 1和对照外植体相比,MPA处理后总软骨DNA减少,TA处理后增加。

结论

MPA和TA并未抵消IL - 1的负面影响,也未将软骨代谢维持在对照水平。较低剂量的MPA和TA对软骨代谢的损害并不小于较高剂量。TA对软骨代谢的危害似乎并不小于MPA。本研究结果与类似体内研究的结果不同。

潜在意义

本研究中使用的马匹数量较少,限制了将这些结果外推至马群;然而,本研究也对该体外模型的临床相关性提出了质疑。

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