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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。
Objective To study the effects of estrogen on the pathogenesis of collagen-induced arthritis (CIA) and the effects of pegylated sialyl amidase 4 (PADI4) and TXNDC5 on it. Methods Twenty-nine male Lewis rats were randomly divided into 4 groups: normal control group (n = 6), CIA model group (n = 8), estrogen intervention group Hormone group (Group E, n = 7). Subcutaneous injection of bovine type Ⅱ collagen (C Ⅱ) to establish CIA model, during which estrogen intervention. The levels of TNFα, IL-1β and VEGF in serum were detected by ELISA. The synovial membrane was detected by immunohistochemistry, Western-blot and real-time PCR In PADI4 and TXNDC5 expression. Results Compared with group C, the onset time of arthritis in group T was delayed by about 6 days (P = 0.045), and there was no significant difference in the degree of inflammation and morbidity. The levels of TNFα and IL-1β were not significantly changed, while the levels of VEGF = 0.023). Synovial tissue in T group proliferated abnormally with capillary proliferation. PADI4 mainly expressed in synovial lining and infiltrating inflammatory cells. TXNDC5 mainly distributed in synovial lining and capillary endothelial cells. Estrogen significantly stimulated the expression of TXNDC5 in CIA synovium (P <0.05), but had no significant effect on the expression of PADI4. Conclusion Although estrogen can delay the onset of arthritis, estrogen may stimulate synovial capillary hyperplasia in rheumatoid arthritis (RA) by up-regulating TXNDC5 expression.