滑膜细胞凋亡在胶原诱导性关节炎大鼠发病机制中的意义

The significance of synoviocyte apoptosis in pathogenesis of collagen-inducing arthritis in rats

目的研究滑膜细胞凋亡在胶原诱导性关节炎（CIA）大鼠发病机制中的作用。方法将30只健康雄性Wistar大鼠随机分为造模组（20只）、正常对照组（10只，简称正常组）；造模组采用牛Ⅱ型胶原诱导建立CIA模型，造模成功后随机选取10只作为模型组。观察4周后，取各组滑膜标本，采用苏木素-伊红（HE）染色评价滑膜炎性细胞浸润及增生情况，并运用透射电镜、流式细胞术及细胞凋亡原位检测试剂（TUNEL）法检测滑膜细胞凋亡。结果HE病理结果显示：模型组的滑膜炎性细胞浸润和增生程度积分均较正常组显著增加（P〈0．01）。透射电镜检测结果显示：正常组可见滑膜细胞核膜皱缩，核染色质分布不均匀；模型组可见滑膜细胞呈梭形，细胞膜皱缩，细胞体积变小与邻近细胞分离，核内见染色质浓缩。流式细胞术、TUNEL法检测结果显示：模型组大鼠滑膜细胞凋亡率和凋亡指数均较正常组明显降低（P〈0．05或0．01）。结论CIA大鼠滑膜细胞增殖、滑膜细胞凋亡减少可能是导致CIA的发病机制之一。

Objective To investigate apoptosis of synoviocytes in pathogenesis of collagen-inducing arthritis （CIA） in rats. Methods Twenty Wistar rats were randomly divided into CIA group and control group （n=10 in each）. The CIA model was established by injection of type II collagen of bovine （BC II ） emulsion in the tail of rats. After 4 weeks, the inflammatory celt infiltrating and hyperplasia were determined by HE staining, the apoptosis of synoviocytes was determined by TUNEL method, flow cytometric analysis and electron microscopy. Results Histopathology demonstrated that the degree of inflammatory cell infiltrating and hyperplasia in CIA group was more predominant than in control group （P〈0.01）. Electron microscopy showed crenation in the nuclear membrane of synoviocytes and heterogeneous distribution of chromatin in control group, while in CIA group the shape of synoviocytes was spindle with crenation in the membrane of synoviocytes, the cell size was reduced and synoviocytes were separated from others and the nucleus chromatin was concentrated. Comparing to control group the apoptosis index of synoviocytes in CIA group was decreased （ P〈0.05 or〈0.01 ）. Conclusion Increased proliferation and reduced apoptosis in synoviocytes may be involved in the pathogenesis of CIA in rats.