几种抗类风湿性关节炎药物对佐剂性关节炎大鼠关节软骨细胞酸敏感离子通道的表达影响及作用

中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (2): 131-137.

几种抗类风湿性关节炎药物对佐剂性关节炎大鼠关节软骨细胞酸敏感离子通道的表达影响及作用

陈飞虎, 袁凤来, 李霞, 吴繁荣, 黄学应, 胡伟, 沈娟, 李俊

安徽医科大学药学院, 合肥 230032, 安徽

收稿日期:2007-10-16 修回日期:2007-11-17 出版日期:2008-02-26 发布日期:2020-10-14
作者简介:陈飞虎, 男, 博士, 教授, 博士生导师, 研究方向:分子药理学。Tel:0551-5161115 　E-mail:cfhchina@sohu.com
基金资助:
国家自然科学基金资助(30572196); 安徽省高等学校省自然科学研究项目(kj2007B034)

Effects of several anti-rheumatoid arthritis drugs on expression of acidsensitive ion channels in articular chondrocytes in rats with adjuvant arthritis

CHEN Fei-hu, YUAN Feng-lai, LI Xia, WU Fan-rong, HUANG Xue-ying, HU Wei, HENG Juan, LI Jun

School of Pharmacy, Anhui Medical University,Hefei 230032, Anhui, China

Received:2007-10-16 Revised:2007-11-17 Online:2008-02-26 Published:2020-10-14

摘要/Abstract

摘要： 目的:观察几种抗类风湿性关节炎(RA)药物对佐剂性关节炎(AA)大鼠关节软骨中的酸敏感离子通道(ASICs)表达的影响, 探讨抗RA药物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、阿司匹林(50 mg/kg)组、地塞米松(0.2 mg/kg)组、雷公藤多苷(50 mg/kg)组和左旋咪唑(10 mg/kg)组。弗氏完全佐剂(CFA)致炎后第10天起,AA大鼠出现继发性炎症, 此时地塞米松组腹腔注射地塞米松, 其它用药组分别灌胃相应的受试药物, 正常组与模型组灌胃等容量的无菌注射用水, 连续7d。实验结束后, 光学显微镜观察关节病理变化;用半定量RT-PCR和Western blotting分析常用药物对AA大鼠关节软骨细胞中ASICs表达的影响;用半定量RT-PCR方法分析常用药物对AA大鼠关节软骨中的蛋白聚糖体(aggregate proteoglycan, aggrecan)表达的影响;免疫组织化学技术检测常用药物对AA大鼠关节软骨中的Ⅱ型胶原蛋白合成的影响。结果:经过治疗后, 各用药组能明显抑制AA大鼠的继发性足肿胀。阿司匹林能显著抑制AA大鼠关节软骨细胞ASICs的表达, 其它用药组对ASICs无明显抑制作用。各用药组能明显升高AA大鼠关节软骨细胞基质成分Ⅱ型胶原和aggrecan表达量, 其中阿司匹林作用显著。结论:阿司匹林可能通过抑制ASICs的表达而抑制AA大鼠关节软骨的破坏。

关键词: 阿司匹林, 佐剂性关节炎, 软骨, 关节, 离子通道

Abstract: AIM:To observe the effects of several common used drugs on expression of acid-sensitive ion channels (ASICs) in articular cartilage in rats with adjuvant arthritis (AA), and to explore cartilage protection of different medicines in the treatment of rheumatoid arthritis (RA).METHODS:The rats were randomly divided into the normal group, AA model group, aspirin (15 mg/kg) group, dexamethasone (0.2 mg/kg) group, tripterygium wilfordii (50 mg/kg) group and levamisole (10 mg/kg) group. The AA rat model was induced by a single intradermal injection of 100 μL of Freund's complete adjuvant (CFA) on day 0. The volume of rat hind paw was measured by means of Volume Meter. The secondary inflammation of AA rats appeared on the d 10 after intradermal injection of CFA. Intraperitoneal injection of dexamethasone at this time, other drug groups were gavaged corresponding experimental drugs, and the model group and the normal group were administered with the corresponding capacity of sterile water, lasting for seven days. The morphological changes of synovial membrane was observed by light microscope. The quantitative PCRwas used to detect the ASICs and aggrecan mRNA expression in rat articular cartilage. The immunoblotting analyses was used to detect the ASICs protein expression in rat articular cartilage. 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. Aspirin obviously inhibited the expression of ASICs of articular cartilage cells in AA rats, but the inhibitory effects of other drugs were not obvious. The type II collagen and aggrecan expression of cell matrix of articular cartilage was increased significantly by four kinds of drugs, especially aspirin, in AA rats. CONCLUSION:Aspirin may play a protective role in articular cartilage in AA rats by inhibiting expression of ASICs.

Key words: aspirin, adjuvant arthritis, cartilage, articulation, ion channels

中图分类号:

R965

陈飞虎, 袁凤来, 李霞, 吴繁荣, 黄学应, 胡伟, 沈娟, 李俊. 几种抗类风湿性关节炎药物对佐剂性关节炎大鼠关节软骨细胞酸敏感离子通道的表达影响及作用[J]. 中国临床药理学与治疗学, 2008, 13(2): 131-137.

CHEN Fei-hu, YUAN Feng-lai, LI Xia, WU Fan-rong, HUANG Xue-ying, HU Wei, HENG Juan, LI Jun. Effects of several anti-rheumatoid arthritis drugs on expression of acidsensitive ion channels in articular chondrocytes in rats with adjuvant arthritis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(2): 131-137.

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