佐剂关节炎大鼠心功能变化与细胞因子、调节T细胞和Foxp3表达的相关性

摘要

Objective: To observe paw swelling (E) and arthritis index (AI), cardiac function, cytokines, regulatory T cells (Tregs) and the expression of Foxp3 in rats with adjuvant arthritis (AA). Methods: Twenty-four Wistar male rats were randomly divided into normal control (NC) group and AA model group, 12 in each group.The AA model was established by intradermal injection of Freund's complete adjuvant (FCA) in the right paw in the AA model group. One day before, and 18 and 32 days after AA establishment, body weight, E and Al were determined, and at the 48th day, cardiac function, peripheral blood interleukin-6 (II.-6), IL-10, IL-17, tumor necrosis factor alpha (TNF-α), Tregs, the expression of Foxp3 in the spleen were tested. Results: (1) Compared with NC group, HR, cardiac mass index (HI), left vent ricular end systolic pressure (LVSP) were significantly increased,left ventricular pressure ±dp/dtmax was significantly decreased, body weight was significantly decreased, E and Al were significantly increased, serum TNF-α, IL-17 and IL-6 levels were significantly increased, and the IL-10 level was significantly decreased, the expression of CD4 +Tregs, CD25 +Tregs, CD4 +CD25 +Tregs, and that of Foxp3 in the spleen were significantly down-regulated in AA model group; (2) Spearman correlation analysis showed that, cardiac hemodynamic function parameters were significantly correlated with Al, cytokines, Tregs and Foxp3 (P＜ 0.05 or P＜ 0.01 ). Conclusion: The cardiac function, and the expression of Foxp3, CD4 + CD25 +Tregs were reduced spontaneously in the AA rats with increased E and AI, suggesting inflammation, and the imbalance between Foxp3 and CD4+CD25+ Tregs may be the major factors for cardiac function changes in AA rats.%目的:观察佐剂性关节炎(adjuvant arthritis,AA)大鼠足跖肿胀度(E)、关节炎指数(AI)、心功能、细胞因子、调节T细胞及Foxp3的表达,探讨细胞因子、转录因子Foxp3与调节T细胞(Treg)在AA大鼠心功能改变中的作用机制.方法:24只Wistar雄性大鼠随机分为正常组和模型组(Model组)各12只,Model组大鼠成功复制成AA模型.分别在造模前1 d,造模后18及32 d时检测2组大鼠体质量、E及AI,48 d后检测心功能、外周血细胞因子和肿瘤坏死因子-α(TNF-α)水平、Treg及脾组织Foxp3的表达.结果:与正常组比较,Model组心率(HR)、心脏质量指数(HI)、左室收缩末压(LVSP)显著升高,左室内压上升/下降最大速率(±dp /dtmax)显著降低;体质量明显减轻,E、AI明显增高;血清中TNF-α、IL-17 、IL-6的水平明显升高,IL-10显著降低;CD4+Treg、CD25+Treg、CD4+CD25+Treg的表达及脾组织Foxp3蛋白染色指数、蛋白积分光密度值、Foxp3mRNA、Foxp3蛋白的表达水平均下调明显;Spearman相关分析结果显示,Model组大鼠心功能参数与AI、细胞因子、Treg及Foxp3等指标呈显著相关性(均P<0.05,P<0.01).结论:AA大鼠在E、及AI升高的同时出现心功能及Foxp3、CD4+CD25+Treg表达降低,提示炎症、Foxp3、CD4+CD25+Treg表达的失衡可能为AA大鼠心功能改变的重要因素.