摘要
目的:观察常用抗类风湿性关节炎(RA)药物对佐剂性关节炎(AA)大鼠关节软骨基质金属蛋白酶(MMPs)的影响和对关节软骨的保护作用。方法:将大鼠随机分成正常组、AA模型组、双氯芬酸钠(2mg.kg-1)组、地塞米松(0.2mg.kg-1)组、雷公藤多苷(50mg.kg-1)组和左旋咪唑(10mg.kg-1)组。弗氏完全佐剂(CFA)致炎10d,AA大鼠出现继发性炎症,腹腔注射地塞米松,其它用药组分别灌胃受试药物,正常组与模型组灌胃等容量灭菌注射用水,连续7d。光学显微镜观察关节病理变化;用半定量RT-PCR和Western blot法分析药物对AA大鼠关节软骨MMPs表达的影响;免疫组化技术检测药物对AA大鼠关节软骨中Ⅱ型胶原蛋白合成的影响。结果:各用药组均能明显抑制AA大鼠继发性足肿胀;地塞米松和雷公藤多苷均能显著抑制AA大鼠关节软骨MMPs mRNA和MMPs蛋白表达,双氯芬酸钠和左旋咪唑组对MMPs无明显作用;地塞米松和雷公藤多苷均能升高AA大鼠关节软骨细胞基质成分Ⅱ型胶原表达量,双氯芬酸钠和左旋咪唑对其无明显影响。结论:常用抗RA药物如地塞米松和雷公藤多苷可能通过抑制MMPs的表达进而保护关节软骨的破坏,而双氯芬酸钠和左旋咪唑对MMPs无作用。
OBJECTIVE To observe the Effect of several common drugs on expression of MMPs in articular cartilage in rat with AA, and to explore cartilage protection of several kinds of medicines in the treatment of rheumatoid arthritis（RA）. METHODS The rats were randomly divided into the normal group, AA model group, diclofenac sodium（2 mg·kg^-1）group, dexamethasone（0. 2 mg·kg^-1 ）group, glycosides of tripterygium wilfordii（50 mg·kg^-1 ） group and levamisole（10 mg·kg^-1）group. Adjuvant arthritis rat model was induced by a single intradermal injection of 100μL of Freund＇s complete adjuvant（CFA）on d0. The secondary inflammation of adjuvant-induced arthritis（AA）rats appeared on the dl0 after intradermal injection of CFA. Intraperitoneal injection of dexamethasone at this time, other drug groups were gavaged corresponding test drugs, and the model group and the normal group gavaged the corresponding capacity sterile water, lasting for 7 days. The morphological changes of synovial membrane was observed by light microscope. Quantitative PCR were used to detect MMPs. The expression of type Ⅱ collagen was measured by immunohistochemical method. RESULTS It was found that the secondary paw swelling was inhibited significantly in AA rats. Dexamethasone and glycosides of tripterygium wilfordii may inhibit obviously the expression of MMPs mRNA and protein of articular cartilage in AA rats, but the inhibitory effect of other drugs may not be obvious. Type Ⅱ collagen expression of cell matrix of articular cartilage can be increased significantly by two kinds of drugs, especially dexamethasone and glycosides of tripterygium wilfordii in AA rats. CONCLUSION Commonly used anti-rheumatoid arthritis drugs such as dexamethasone and glycosides of tripterygium wilfordii probably protect the articular cartilage damage by inhibiting the expression of MMPs, while diclofenac sodium and dexamethasone had no inhibitory effect.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2008年第11期882-886,共5页
Chinese Journal of Hospital Pharmacy
关键词
基质金属蛋白酶
佐剂性关节炎
关节软骨
matrix metalloproteinases
adjuvant arthritis
cartilage, Articular
