补肾祛寒治尪汤联合甲氨蝶呤对大鼠胶原诱导关节炎模型的抗炎作用研究

Research on anti-inflammatory effect of kidney-supplementing cold-dispelling Zhiwang Decoction combined with methotrexate on CIA model rats

目的评估补肾祛寒治尪汤(简称"治尪汤")联合甲氨蝶呤(MTX)对大鼠胶原诱导关节炎(CIA)模型的作用及高频超声在大鼠关节炎评估中的应用。方法 SD大鼠随机分为正常组、模型组、MTX组、治尪汤低剂量联合组、治尪汤高剂量联合组;除正常组外,其余大鼠分别于第1、7天尾部注射浓度为2 mg/mL的Ⅱ胶原乳剂50μL建立CIA模型;第8天开始给药21 d,检测足趾厚度,进行关节炎指数评分,并采用高频超声评估大鼠关节滑膜炎。结果造模后,各组大鼠足趾厚度较正常组明显增厚(P<0.01),第19天治尪汤高剂量联合组大鼠足趾厚度小于模型组(P<0.05);AI评分方面,第13天治尪汤高剂量联合组大鼠AI评分小于模型组(P<0.01);各组与正常组比较滑膜显著增厚,治尪汤低、高剂量联合组与模型组比较滑膜厚度显著降低,治尪汤高剂量联合组较MTX组滑膜厚度显著降低(P<0.05,P<0.01)。结论高频超声适用于大鼠CIA模型滑膜炎的评估,敏感性优于足趾厚度检测和AI评分,高剂量治尪汤与MTX联用对改善CIA大鼠关节炎有协同增效作用。

Objective To access the anti-inflammatory effect of kidney-supplementing cold-dispelling Zhiwang Decoction(Zhiwang Decoction) combined with methotrexate(MTX) on collagen-induced arthritis(CIA) model rats and the performance of high frequency ultrasound in the evaluation of arthritis in rats. Methods SD rats were randomly divided into 5 groups: normal group, model group, MTX group, low-dose of Zhiwang Decoction combined group and high-dose of Zhiwang Decoction combined group. Except for the normal group, rats of the other groups were injected in the tail with 50 μL collagen Ⅱ emulsion of 2 mg/mL on the 7 th and 14 th day of rearing respectively. A total of 21 days of administration began on the 8 th day. Toe thickness was measured, arthritis index(AI) was scored and ankle synovitis was evaluated by high-frequency gray-scale ultrasound in rats. Results After modeling, the toe thickness of each group was significantly thicker than that of the normal group(P<0.01). on the 19 th day, the toe thickness of the high-dose combined group was thinner than that of the model group(P<0.05). In terms of AI score, on the 13 th day, the AI score of the high-dose combined group was lower than that of the model group(P<0.01). Evaluated by the ultrasound, the synovial thickness of each group was significantly thicker than that of the normal group, the synovium of the low-dose and high-dose groups was significantly thinner than that of the model group, and the synovium of the high-dose group was significantly thinner than that of the MTX group(P<0.05, p < 0.01). Conclusion High-frequency ultrasound is suitable for the evaluation of synovitis in CIA model rats,and its sensitivity is better than toe thickness and AI score. High-dose Zhiwang Decoction combined with MTX has a synergistic effect on improving arthritis in CIA rats.