雌激素对胶原诱导关节炎动物模型发病过程的作用

山东大学学报(医学版) ›› 2010, Vol. 48 ›› Issue (8): 54-59.

雌激素对胶原诱导关节炎动物模型发病过程的作用

韦超1,吴围屏1,赵燕1,王林1,闫新峰2 ,常晓天1

1.山东省医药生物技术研究中心，济南 250062； 2.山东大学附属千佛山医院骨关节中心，济南 250014

收稿日期:2009-12-22 出版日期:2010-08-16 发布日期:2010-08-16
通讯作者: 常晓天（1964- ），男，博士，教授，硕士生导师，主要从事类风湿关节炎致病基因病理机制研究。E-mail: chagxt@163.com
作者简介:韦超（1982- ），男，硕士研究生，主要从事类风湿关节炎致病基因病理机制研究。
基金资助:
国家自然科学基金资助项目（30972720）；山东省自然科学基金资助项目（Y2008C130）

Effects of estrogen on the disease development in the collagen-induced arthritis animal models

WEI Chao1, WU Wei-ping1, ZHAO Yan1, WANG Lin1, YAN Xin-feng2, CHANG Xiao-tian1

1. Shandong Medicinal Biotechnology Center, Jinan 250062, China;
2. Orthopedic Center, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, China

Received:2009-12-22 Online:2010-08-16 Published:2010-08-16

摘要/Abstract

摘要：

目的研究雌激素对胶原诱导关节炎（CIA）发病过程的影响以及对肽基精酰胺脱亚胺基酶4（PADI4）和TXNDC5表达的影响。方法雄性Lewis大鼠29只随机分成4组：正常对照组（H组，n=6）、CIA模型组（C组，n=8）、雌激素干预组（T组，n=8）和雌激素组（E组，n=7）。皮下注射牛Ⅱ型胶原（CⅡ）建立CIA模型，其间进行雌激素干预。ELISA法检测血清中肿瘤坏死因子α（TNFα）、白介素-1β(IL-1β)和血管内皮生长因子（VEGF）的含量；免疫组织化学法、Western-blot法和real-time PCR法检测滑膜中PADI4和TXNDC5的表达。结果与C组相比，T组的关节炎发病时间约延缓6d（P=0.045），炎症程度和发病率无显著差异；TNFα和IL-1β的含量无明显改变，VEGF含量明显升高（P=0.023）；T组滑膜组织异常增殖并伴毛细血管增生，PADI4主要表达于滑膜衬里及侵润的炎性细胞，TXNDC5主要分布于滑膜衬里及毛细血管的内皮细胞。雌激素明显刺激CIA滑膜中TXNDC5的表达（P＜0.05），但对PADI4的表达无显著影响。结论雌激素虽然能延缓关节炎的发病时间，但可能通过上调TXNDC5的表达，刺激类风湿关节炎（RA）滑膜毛细血管增生。

关键词: 类风湿关节炎；胶原诱导关节炎；雌激素；肽基精氨酸脱亚胺基酶4

Abstract:

Objective To investigate the effects of estrogen on the disease development and the expressions of peptidylarginine deiminase 4 (PADI4) and thioredoxin domain containing protein 5 (TXNDC5) in collagen induced arthritis (CIA) models. Methods Twenty-nine male Lewis rats were randomly divided into four groups: the healthy control group (group H, n=6）, the CIA group (group C, n=8), the CIA group treated with estrogen (group T, n=8) and the estrogen group（group E, n=7). CIA was induced subcutaneously with bovine type Ⅱcollagen (CⅡ) and estrogen treatment was operated during CⅡsensitization. ELISA was used to measure the levels of TNFα, IL-1β and VEGF in serum samples. Immunohistochemisty, Western-blot and real-time PCR were applied to detect the expressions of PADI4 and TXNDC5 in synovial membranes. Results Compared with group C, the onset of CIA significantly delayed for 6 days (P=0.045) with no effects on inflammatory severity and incidence rates of the disease in group T; the serum levels of TNFαand IL-1βwere not evidently altered, but the level of VEGF was considerably increased (P=0.023). Synovial tissues in group T showed more hyperplasia with angiogenesis, in which PADI4 was mainly expressed in the lining and infiltrated inflammatory cells of synovium and TXNDC5 was mainly presented in the lining of synovium and endotheliocytes of capillaries. Estrogen pronouncedly stimulates the expression of TXNDC5 (P<0.05) rather than the expression of PADI4. Conclusion Although estrogen can delay the onset of arthritis, it may stimulate angiogenesis in rheumatoid arthritis synovium via the up-regulation of TXNDC5.

Key words: Rheumatoid arthritis; Collagen-induced arthritis; Estrogen; Peptidylarginine deiminase 4

中图分类号:

韦超1,吴围屏1,赵燕1,王林1,闫新峰2 ,常晓天1. 雌激素对胶原诱导关节炎动物模型发病过程的作用[J]. 山东大学学报(医学版), 2010, 48(8): 54-59.

WEI Chao1, WU Wei-ping1, ZHAO Yan1, WANG Lin1, YAN Xin-feng2, CHANG Xiao-tian1 . Effects of estrogen on the disease development in the collagen-induced arthritis animal models[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(8): 54-59.

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