摘要
目的 探讨Janus激酶／信号转导子与转录激活子（JAK／STAT）信号通路对类风湿关节炎（RA）大鼠滑膜细胞凋亡相关基因表达的影响。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AG4901、5、10mg·kg^-^1·d^-^1腹腔注射，对照组及模型组予以生理盐水1ml/d腹腔注射。应用单因素方差分析观察应用JAK／STAT阻断剂前后滑膜细胞Bcl-2、Bcl-xl、Bax mRNA及蛋白表达情况。结果 CIA模型组Bcl-2、Bcl-xl mRNA及蛋白表达水平较对照组明显增高（0．931±0．035与0．351±0．024，0．920±0．037与0．271±0．029，0．322±0．047与0．230±0．031），Bax表达轻微上调；应用JAK／STAT阻断剂后Bcl-2、Bcl-xl基因及蛋白质表达水平明显下降，而Bax的基因及蛋白质水平明显升高。结论 在RA发病过程抗凋亡因子呈明显高表达状态，而JAK／STAT通路对凋亡调控基因具有直接的调节作用。
Objective To explore the effect of the JAK/STAT signal pathway on the apoptosis-related gene in the synovial tissue of rat rheumatoid arthritis （RA）. Methods Fifty rat models of collagen-induced arthritis, whose arthritis index was more than 2, were divided into the model group, the low dose of AG490 group, the medium close of AG490 group and the high dose of AG490 group. In addition, 6 rats were treated as normal control group. And they were given normal sodium, AG490 1, 5 and 10 mg·kg^-^1·d^-^1 by intraperitoneal injection. Then, the arthritis index and the change of apoptosis-related genes were compared. Multiple-sample average was analyzed by single-factor x^2 test and LSD-t or Tamhane＇s T 2 test were used for two-two comparison. Results The arthritis index of the model group increased evidently, and the apoptosis inhibitor Bcl-2, Bcl-xl gene and protein expression was up-regulated, which was significantly different when compared with that of the control group （0.931±0.035 vs 0.351±0.024, 0.920±0.037 vs 0.271±0.029, 0.322±0.047 vs 0.230±0.031）. The expression of apoptosis promoting factor Bax was slightly up-regulated. The blockage of JAK/STAT pathway could down-regulate the expression levels of the gene and protein of survivins Bcl-2 and Bcl-xl, and up-regulate the gene and protein expressions of Bax. Conclusion In the process of RA development, apoptosis inhibitor Bcl-2, Bcl-xl gene and protein expression is up-regulated. JAK/STAT signal transduction pathway regulates the apoptosis process.
出处
《中华风湿病学杂志》
CAS
CSCD
北大核心
2011年第2期111-115,共5页
Chinese Journal of Rheumatology
