摘要
目的探讨CD4+CD25+调节性T细胞在实验性关节炎中的作用及其机制。方法①将大鼠随机分为模型组和对照组,根据文献建立模型,在建模成功后的不同时间点取脾脏关节滑膜。②采取反转录-聚合酶链反应(RT-PCR)的方法检测大鼠脾脏Foxp3 mRNA的表达,采取免疫组织化学半定量法检测脾脏和滑膜转化生长因子(TGF)-β1的表达。结果①Foxp3 mRNA在实验性关节炎大鼠脾脏中的动态表达过程在关节炎急性期表达最高,慢性期逐渐下降,均高于对照组(P<0.01)。②TGF-β1在实验性关节炎大鼠脾脏中的动态表达过程为逐渐增高,到关节炎急性期时,表达降低,慢性期升高,均高于对照组(P<0.01)。③实验性关节炎大鼠脾脏Foxp3 mRNA的表达与TGF-β1的表达呈线性负相关(r=0.8124)。④实验性关节炎大鼠关节滑膜TGF-β1的动态表达过程为逐渐增高,到慢性期下降,均高于对照组(P<0.01)。⑤TGF-β1在实验性关节炎大鼠滑膜中的表达与关节的严重程度有相关关系(与关节炎病理评分的r=0.9474)。结论①在实验性关节炎大鼠中,CD4+CD25+调节性T细胞的增减与炎症反应的强弱呈正相关,可能因其功能存在缺陷,不能有效抑制机体的自身免疫反应。②抑制性因子TGF-β1产生相对不足并且分泌延迟可能是造成实验性关节炎大鼠脾脏CD4+CD25+调节性T细胞功能缺陷的原因之一。③在实验性关节炎大鼠中Foxp3表达基因是否存在缺陷,有待进一步研究证实。
Objective To investigate the roles and of CD4^＋CD25^＋ regulatory T cells in collagen-induced arthritis and their underlying mechanisms. Methods Wistar rats were randomized into the control and experimental groups. Models of collagen-induced arthritis were established as described in publications while controls received only saline injections. At various time spots, splenic and synovial tissues were obtained from rat models and also from controls. The expression of Foxp3 mRNA in the spleen was detected by reverse transcription polymerase chain reaction, and the ex pression of transforming growth factor beta 1 （TGF-β1） in the spleen and synovium by immunohistochemistry. Results As compared with the controls, the expressions of Foxp3 mRNA in the spleen tissue and TGF-β1 in the spleen and synovium were found to be significantly up-regulated （all P〈0.01）. The expression of Foxp3 mRNA in spleen tissue was most intense during the acute stage and gradually declining during the chronic stage, the expression of TGF-β1 in the spleen decreased during the acute stage and gradually enhanced during the chronic stage; and that in the synovium was enhanced during the acute stage and gradually attenuated during the chronic stage. Expression of synovial TGF-β1 was shown to be associated the severity of disease （as assessed by pathological score, r=0.9474）, and negatively correlated with the expression of Foxp3 mRNA （r=0.8124）. Conclusion The function of CD4^＋CD25^＋ regulatory T cells was lowered in rats with artificial arthritis, which may be attributable to abnormal expression of Foxp3 mRNA in these cells. This may lead to reduced production of TGF-β1 and inadequate suppression of autoimmune response in collagen-induced arthritis. Further studies are needed to show whether Foxp3 gene is defective in this condition.
出处
《中国药物与临床》
CAS
2008年第11期880-884,922,共6页
Chinese Remedies & Clinics
