寒冷刺激引起关节损伤实验研究

Experimental Study on Joint Injury Caused by Cold Stimulation

目的观察间断性寒冷刺激引起小鼠关节炎病变的情况。方法将20只8周龄昆明小鼠随机分为正常对照组和寒冷刺激组,每组10只。对照组小鼠自由饮食,无特殊处理。寒冷刺激组小鼠每天固定时间被放置于底层铺满冰袋的小鼠笼中2 h,寒冷刺激共处理12周。每周测量小鼠体重和后踝关节以下体积,寒冷刺激处理结束后脱颈处死小鼠,取其左后腿趾间关节、跖趾关节、踝关节进行组织固定、包埋、切片,HE染色观察各关节病理变化。剥去小鼠右后腿皮肤,提取踝关节组织匀浆,检测匀浆液类风湿因子(reumatoid factor,RF)、C-反应蛋白(C-reaction protein,CRP)的水平。结果寒冷刺激对小鼠体重无明显影响(P>0.05),寒冷刺激使小鼠后爪组织体积显著增加(P<0.05)。趾间关节、跖趾关节、踝关节HE染色显示寒冷刺激后,小鼠关节组织水肿,轻度炎症浸润、滑膜增生,但未见明显血管翳、软骨和骨侵蚀等病理变化。寒冷刺激后,雌、雄性小鼠踝关节组织匀浆液CRP水平明显升高(P<0.05,P<0.001),RF水平无明显变化(P>0.05)。结论间断性寒冷刺激可以引起小鼠趾间关节、跖趾关节、踝关节等关节炎性肿胀,但炎性细胞浸润少、浸润程度轻。此动物模型可作为一种以寒性为特征的不同于类风湿性关节炎等热性关节炎表现的新关节炎模型。

Objective To observe the condition of arthritis in mice caused by intermittent cold stimulation.Methods Twenty Kunming mice aged 8 weeks were randomly divided into normal control group and cold stimulation group,with ten in each group.The control group were free to eat with no special treatment,while the cold-stimulated mice were placed in ice-packed cages for 2 h,per day at a fixed time.The cold stimulation was treated for 12 weeks.The weight of the mice and the volume below the posterior ankle were measured weekly.After the cold stimulation,the mice were removed from the neck and killed.The left hind leg interphalangeal joint,metatarsophalangeal joint and ankle joint were fixed,embedded and sliced.HE staining was used to observe the pathological changes of each joint.The skin of the right hind leg of the mice was stripped and the ankle tissue homogenate was extracted to detect the level of rheumatoid factor(RF)and C-reactive protein(CRP).Results Cold stimulation had no obvious effect on the body weight of mice(P>0.05).And cold stimulation had significant increase in the volume of posterior paw tissue in mice(P<0.05).HE staining of interphalangeal joint,metatarsophalangeal joint and ankle joint showed tissue edema,mild inflammatory infiltration,synovial hyperplasia.But no obvious pathological changes such as pannus,cartilage and bone invasion were found.The level of CRP in ankle tissue homogenate increased significantly by cold stimulation in both female and male mice(P<0.05,P<0.001),with no obvious influence on the level of RF(P>0.05).Conclusion Intermittent cold stimulation can cause inflammatory swelling of interphalangeal joint,metatarsophalangeal joint and ankle joint in mice.But the infiltration of inflammatory cells is less,and the degree of infiltration is light.It can be used as a new arthritis model characterized by cold,which is different from that of rheumatoid arthritis.