摘要目的 探讨Janus激酶信号转导子与转录激活子(JAK/STAT)信号通路阻断剂AG490对类风湿关节炎(RA)大鼠滑膜组织天冬氨酸特异性半胱氨酸蛋白酶-3(Caspase-3)表达的影响.方法 雄性Wistar大鼠50只,除对照组6只外,其余均建立胶原诱导的关节炎(CIA)模型,关节炎指数＞2分的大鼠再随机分为CIA模型组,JAK/STAT阻断剂低、中、高剂量组,每组6只.在关节炎开始后,阻断剂组分别予以AG490 1、5、10 mg,kg-1·1d-1腹腔注射,对照组及模型组予以0.9％氯化钠注射液1ml/d腹腔注射.观察应用AG490前后大鼠足趾容积、关节组织病理学评分及滑膜组织Caspase-3表达情况.应用单因素方差分析对结果进行统计.结果 CIA模型组足趾容积及病理评分明显高于对照组,同时在对照组未见可探测到水平的Caspase-3阳性表达条带,而模型组其表达水平略有升高；经过应用不同剂量AG490后,大鼠关节肿胀较模型组明显改善,组织病理评分AG490中、高剂量组(分另为2.7±0.8,1.8±0.9)较模型组(4.3±1.2)明显降低,差异均有统计学意义(P＜0.01),而Caspase-3表达AG490低、中、高剂量组(分别为1.90±0.15,3.13±0.33,3.56±0.34)较模型组(1.48±0.18)明显增高,差异均有统计学意义(P＜0.05或P＜0.01).结论 JAK/STAT信号通路阻断剂AG490可上调Caspase-3的表达,明显改善RA的病理过程.

abstractsObjective To explore the effect of blocking the JAK/STAT signal pathway on the activity of Caspase-3 in the synovial tissue of rheumatoid arthritis rats.Methods Fifty rat models of collageninduced arthritis,which had arthritis index more than 2 were divided into the model group,the low dosage of AG490 group,the medium dosage of AG490 group and high dosage of AG490 group.Inaddition,6 rats were treated as normal control group.Normal saline,AG490 1,5,10 mg·kg-1 ·d-1 were given by intraperitoneal injection.Then the volume claws and pathologic scores of the rat models were recorded and the activity of Caspase-3 in the synovial tissue were compared.The results were analyzed by one-way ANOVA and LSD-t or Tamhane's T2 test.Results The arthritis of the CIA models progressed fast,the volume of the claws and the pathological score of them were significantly higher than those of the control group.At the same time,no Caspase-3 positive express could be detected in the control group,while the model group had slightly increased expression.After different dosages of AG490 were applied,the swollen of joints was significantly improved compared with the model group.The histopathological score of the medium AG490 dosage of group and high dosage group (2.7±0.8,1.8+0.9) were remarkably decreased than those of the model group (4.3+1.2),the differences were statistically significant (P＜0.01).In addition,the Caspase-3 expression in the low,medium and high AG490 dosage group ( 1.90±0.15,3.13±0.33,3.56+0.34) was significantly higher than that of the model group (1.48±0.18) (P＜0.05 or P＜0.01 ).Conclusion Blocking JAK/STAT signal pathway can increase the activity of Caspase-3,reduce the excessive proliferation of synovial tissue,and improve arthritis symptoms.