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目的:复制符合中医证候特点的类风湿关节炎(RA)寒证动物模型并对其进行评价。方法:20只雌性Wistar大鼠,随机分为2组:一组复制胶原诱导性关节炎(CIA)大鼠模型;一组在复制CIA模型的基础上应用动物实验箱,从初次免疫开始连续28d给予风寒湿刺激。期间评价两组大鼠关节炎指数(AI)、足肿胀排水体积、关节疼痛阈值、外周关节体表温度、血流变血液黏度及凝血因子等。结果:两组发病率均为100%(10/10),CIA组成模率为75.00%(6/8),CIA寒证组成模率为77.78%(7/9),两组差异无统计学意义(χ2=0.0182,P=0.893)。但CIA寒证组左足排水体积在造模后14d与基线有差异,而CIA组在造模后21d与基线有差异(P<0.05)。两组大鼠造模后14d双足踝部肤温均升高,在造模后21d均有不同程度降低,组内比较两组各时间点差异均有统计学意义(P<0.05)。CIA寒证组在造模后21d左足体表温度显著低于CIA组(P<0.05)。两组后足关节的疼痛阈值在各个时间点差异无统计学意义;两组左足在造模后21d热板刺激反应时间缩短,疼痛阈值降低;在造模28d后疼痛阈值升高(P<0.05)。CIA寒证组中剪切率(50s-1、30s-1)和低剪切率(1s-1)下的血液黏度值显著升高(P<0.05)。CIA寒证组凝血酶凝结时间显著降低(P<0.05),其余剪切率下血液黏度和凝血因子在两组间差异无统计学意义。结论:CIA模型基础上联合风寒湿刺激,可以诱导出稳定可靠、符合中医证候特点的RA寒证动物模型。
OBJECTIVE: To copy and evaluate the rheumatoid arthritis (RA) cold syndrome animal model which accords with TCM syndrome characteristics. Methods: Twenty female Wistar rats were randomly divided into 2 groups: a group of rats with collagen-induced arthritis (CIA); one group was replicated CIA model based on the use of animal experiment box, starting from the first immunization for 28 days Give cold and wet stimulation. During the evaluation of the two groups of rats arthritis index (AI), foot swelling volume, joint pain threshold, peripheral surface temperature, blood viscosity and blood coagulation factors. Results: The morbidity of the two groups was 100% (10/10), the rate of formation of CIA was 75.00% (6/8), the rate of formation of CIA was 77.78% (7/9), there was no significant difference between the two groups Significance (χ2 = 0.0182, P = 0.893). However, the volume of left foot drainage in CIA cold group differed from baseline at 14 days after modeling, while CIA group differed from baseline at 21 days after modeling (P <0.05). The skin temperature of both ankle and foot increased after 14 days of modeling in both groups, and all decreased to some extent 21 days after modeling. There were significant differences between two groups at different time points (P <0.05). The temperature of left foot body in CIA cold syndrome group was significantly lower than that of CIA group 21 days after modeling (P <0.05). There was no significant difference in pain threshold between the two groups at each time point. The left foot of the two groups reduced the time of hot plate stimulation and the threshold of pain decreased on the 21st day after modeling, and the threshold of pain increased 28 days after the model was established (P <0.05 ). The blood viscosity of CIA cold group was significantly increased at shear rates (50s-1, 30s-1) and low shear rate (1s-1) (P <0.05). The thrombin clotting time in CIA cold syndrome group was significantly lower (P <0.05). The blood viscosity and clotting factor in the other shear rates were not significantly different between the two groups. Conclusion: Based on the CIA model combined with cold and wet stimulation, a stable and reliable animal model of RA cold syndrome can be induced which is consistent with TCM syndromes.