Ratkay L G, Zhang D, Tonzetich J, Levy J G, Waterfield J D
Department of Oral Biology, Faculty of Dentistry, University of British Columbia, Vancouver, Canada.
Clin Exp Immunol. 1994 Oct;98(1):52-9. doi: 10.1111/j.1365-2249.1994.tb06606.x.
Sixty-eight percent of female MRL-lpr mice developed a post-partum exacerbation of their mild spontaneous arthritis within 30 days of parturition. The flare became evident between 5 and 15 days after delivery. Histologically it was characterized by a significant increase of subsynovial inflammation and synovial hyperplasia without changes in the level of cartilage and bone erosion. Immunohistologically, marked subsynovial and frequent synovial staining of MHC class II bearing cells was noted, along with the sporadic presence of CD3, CD4, and CD43 receptor-bearing cells in the subsynovium. Injection of physiological levels (0.08 mg/kg) of estradiol on days 2, 3, 9, 15 and 20 post-partum delayed and reduced the flare to 23% of the animals. Administration of pharmacological amounts (0.4 mg/kg per day for 2 weeks following Freund's complete adjuvant injection) prevented adjuvant-enhanced arthritis, reducing the incidence from 67% to the baseline 21% level. Deleterious changes in the underlying systemic lupus erythematosus (SLE), as demonstrated by proteinuria and mortality rate increases, were elicited only by the employed pharmacological amounts of estradiol. These results indicate that the MRL-lpr mice might serve as a model for post-partum flare of arthritis in SLE and rheumatoid arthritis by providing an approach to study the complexity of the effects of pregnancy on autoimmune diseases, and to obtain further evidence for the involvement of oestrogen in arthritis.
68%的雌性MRL-lpr小鼠在分娩后30天内出现轻度自发性关节炎的产后加重。产后5至15天症状明显加重。组织学上，其特征是滑膜下炎症和滑膜增生显著增加，而软骨和骨侵蚀程度无变化。免疫组织学上，观察到滑膜下显著且滑膜频繁出现携带MHC II类分子的细胞染色，同时在滑膜下偶见携带CD3、CD4和CD43受体的细胞。产后第2、3、9、15和20天注射生理水平（0.08 mg/kg）的雌二醇可延迟症状加重，并将出现症状加重的动物比例降至23%。给予药理剂量（弗氏完全佐剂注射后连续2周每天0.4 mg/kg）可预防佐剂增强性关节炎，将发病率从67%降至基线水平21%。仅所使用的药理剂量的雌二醇会引发潜在系统性红斑狼疮（SLE）的有害变化，表现为蛋白尿和死亡率增加。这些结果表明，MRL-lpr小鼠可作为SLE和类风湿关节炎中关节炎产后加重的模型，为研究妊娠对自身免疫性疾病影响的复杂性提供一种方法，并为雌激素参与关节炎提供进一步证据。
