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地塞米松治疗对大鼠关节软骨超微结构的剂量相关效应。

Dose related effects of dexamethasone treatment on the ultrastructure of articular cartilage in rats.

作者信息

Podbielski A, Raiss R

出版信息

Agents Actions. 1986 Jan;17(3-4):322-4. doi: 10.1007/BF01982635.

DOI:10.1007/BF01982635
PMID:3962777
Abstract

Corticosteroid administration is known to cause degenerative changes in articular cartilage interfering with the cell metabolism of chondrocytes. The present study analyzes the ultrastructural changes in chondrocytes after systemic dexamethasone acetate treatment in relation to dosage, using a standardized morphometrical method. Five male Wistar rats of 300 g body weight in each experimental group were subjected to 3, 4 and 5 mg dexamethasone acetate by intramuscular injections of 1 mg per week. 1000 electron micrographs of single chondrocytes in the middle zone of hyaline cartilage from the knee joints were evaluated with standardized morphometry and nonparametric statistics. With increasing dexamethasone dosage the amount of rough endoplasmic reticulum and Golgi apparatus decreased. Considerably increased glycogen granula and clusters indicated a severe change in glycolytic pathways. Lysosomes duplicated in number. Degenerative changes were also manifested in lipid droplets and myeloid bodies, which, like the amount of microfilaments, exhibited a clear dosage-dependent increase under dexamethasone treatment. The ratio of dead versus living chondrocytes increased in relation to dosage up to 25% cell mortality.

摘要

已知给予皮质类固醇会导致关节软骨发生退行性变化,干扰软骨细胞的细胞代谢。本研究采用标准化形态计量学方法,分析全身注射醋酸地塞米松后软骨细胞的超微结构变化与剂量的关系。每个实验组选取5只体重300克的雄性Wistar大鼠,每周肌肉注射1毫克醋酸地塞米松,剂量分别为3毫克、4毫克和5毫克。对膝关节透明软骨中间区单个软骨细胞的1000张电子显微照片进行标准化形态计量学评估和非参数统计。随着地塞米松剂量的增加,粗面内质网和高尔基体的数量减少。糖原颗粒和团块显著增加,表明糖酵解途径发生严重变化。溶酶体数量增加。脂质小滴和髓样体也出现退行性变化,与微丝数量一样,在接受地塞米松治疗后呈现明显的剂量依赖性增加。死亡软骨细胞与存活软骨细胞的比例随剂量增加而升高,细胞死亡率高达25%。

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本文引用的文献

1
Inhibition of cartilage breakdown by hydrocortisone in a tissue culture model of rheumatoid arthritis.在类风湿性关节炎组织培养模型中氢化可的松对软骨分解的抑制作用。
Ann Rheum Dis. 1983 Jun;42(3):323-30. doi: 10.1136/ard.42.3.323.
2
Functions of lysosomes.溶酶体的功能。
Annu Rev Physiol. 1966;28:435-92. doi: 10.1146/annurev.ph.28.030166.002251.
3
Lysosomes.溶酶体
长期暴露于替莫唑胺会影响老年实验大鼠的运动活性和软骨结构。
Biomedicines. 2020 Nov 26;8(12):541. doi: 10.3390/biomedicines8120541.
4
Dexamethasone: chondroprotective corticosteroid or catabolic killer?地塞米松:软骨保护的皮质类固醇还是分解代谢的杀手?
Eur Cell Mater. 2019 Nov 22;38:246-263. doi: 10.22203/eCM.v038a17.
5
Treatment Response Evaluation using Yttrium-90 in Patients with Rheumatoid Arthritis of Knee Joint.使用钇-90评估膝关节类风湿关节炎患者的治疗反应
World J Nucl Med. 2018 Jan-Mar;17(1):3-5. doi: 10.4103/1450-1147.222289.
6
Alterations in certain lysosomal glycohydrolases and cathepsins in rats on dexamethasone administration.给予地塞米松的大鼠体内某些溶酶体糖水解酶和组织蛋白酶的变化。
Mol Cell Biochem. 1996 Jan 26;154(2):165-70. doi: 10.1007/BF00226784.
N Engl J Med. 1965 Nov 11;273(20):1084-90 contd. doi: 10.1056/NEJM196511112732006.
4
A new test method for the standardized evaluation of changes in the ultrastructure of chondrocytes.一种用于标准化评估软骨细胞超微结构变化的新测试方法。
Int J Tissue React. 1985;7(4):273-89.
5
The antinflammatory effects of glucocorticosteroids. A brief review of the literature.糖皮质激素的抗炎作用。文献综述
Inflammation. 1979 Jul;3(3):329-43. doi: 10.1007/BF00914190.