目的：类风湿性关节炎（RA）脾虚证病证结合动物模型的建立。方法：选用6周龄SPF级SD大鼠60只，雌雄各半，除正常对照组大鼠外，采用腹腔注射利血平的方法制作脾虚动物模型，然后采用尾根部皮下注射Ⅱ型胶原与不完全弗氏佐剂混合物的方法诱导出关节炎模型，观察脾虚证RA病证结合动物模型的发病情况，并采用酶联免疫吸附测定法等方法对其机理进行初步探讨。结果：与CIA对照组大鼠相比，采用腹腔注射利血平的方法制作的脾虚证胶原诱导性关节炎（CIA）大鼠关节红肿程度和关节损伤程度明显加重，并且脾虚证CIA组大鼠出现精神萎靡，眯眼，被毛枯疏无光泽，弓背蜷缩，踝关节红肿，倦怠、懒动，喜聚堆，饮食减少，体重下降，稀便等与临床脾虚证相似的症状；与CIA对照组大鼠相比，脾虚证小肠黏膜功能受损：绒毛排列紊乱，数量减少，长短、宽窄不一，被覆上皮可见有多量杯状细胞，肠腔内可见多量剥脱、退变、坏死的绒毛碎片；与CIA对照组大鼠相比，脾虚证CIA大鼠抗Ⅱ型胶原抗体明显升高，且白细胞介素6、白细胞介素10及干扰素γ水平明显升高。结论：脾虚在RA发病过程中起着重要作用，采用利血平方法制作的脾虚证RA动物模型，既有明显的脾虚症状，又有明显的RA特征，说明这种脾虚证RA病证结合模型，能够部份反映脾虚证RA病人的发病特点，具有可行性。利血平法制作的脾虚证CIA大鼠模型可以为RA脾虚证病证结合动物模型提供一个有益的参考。

This study was aimed to establish a disease-syndrome combination rat model of rheumatoid arthritis (RA) with spleen deficiency. A group of 60 six-week-old Sprague-Dawley rats were randomly divided into normal control group and reserpine (RSP) group. Spleen deficiency model rats groups were made by intraperitoneal injection of RSP. Then rats of RSP groups were subcutaneously injected with collagen protein to induce CIA. The incidence of the model was observed and the mechanism was analyzed by enzyme-linked immunosorbent assay (ELISA). The results showed that compared with the CIA normal group, the degree of joint swelling and joint damage was significantly increased in the RSP CIA model. The RSP CIA model rats were noted with spleen deficiency syndrome similar to clinical symptoms, such as appeared apathetic, squinting, sparse dry dull coat, bowed back, swollen ankle, fatigue, lazy move, get together, eating less, weight loss and loose stool. Compared with the CIA control rats, spleen deficiency impaired the function of intestinal mucosa by disordering the intestinal villi, covering large amount of goblet cells in epithelium, and inducing exfoliation, degeneration and necrosis fluff pieces. The content of anti-type Ⅱ collagen antibody, IL-6, IL-10 and IFN-γ was increased. It was concluded that the rat model of RA disease-syndrome combination with spleen deficiency has been established. Spleen deficiency plays a vital role in RA.

科学技术部国家“重大新药创制”科技重大专项（2009ZX09502-019）：基于辨证论治治疗类风湿性关节炎（RA）中药新药药效评价动物模型研制及其应用研究，负责人：吕爱平；科学技术部国家科技支撑计划重点项目（2006BAI08B01-01）：类风湿关节炎证候分类方法及其病证结合动物模型制作与评价方法研究，负责人：鞠大宏；国家自然科学基金项目（30701067）：从HMGB1信号转导探讨肾虚痹证（类风湿关节炎）的发生机理，负责人：肖诚；国家自然科学基金项目（30902000）：基于肾阳虚关节炎大鼠壮骨关节丸毒性反应评价研究，负责人：吕诚。