中文摘要：

目的：初步探讨类风湿关节炎（RA）患者外周血单个核细胞（PBMCs）和滑膜组织中SonicHedge-hog（Shh）信号通路相关因子表达及意义。方法：收集符合1987年美国风湿病学会（ACR）RA分类标准、28个关节疾病活动度评分（DAS28）≥3.2,病情活动RA患者（35例）及年龄、性别相匹配的健康志愿者（35例）外周血2 mL,分离PBMCs,提取总RNA,采用实时荧光定量PCR（real-time PCR）检测Shh信号通路中信号肽Shh、膜受体Ptch1和核转录因子Gli1 mRNA的表达。收集10例病情中度活动（DAS28≥3.2）RA患者的滑膜组织,同时收集5例外伤或半月板损伤（无关节炎）者滑膜组织作为对照组,免疫组化检测Shh、Ptch1和Gli1的蛋白表达情况。结果：RA患者PBMCs中Shh和Gli1 mRNA的相对表达量分别为1.36±1.48和1.15±0.68,对照组上述信号分子的mRNA表达量分别为0.47±0.25和0.49±0.05,2组差异有统计学意义（P〈0.05）,Ptch1 mRNA表达在2组间的差异无统计学意义（P〉0.05）;免疫组化示Shh和Gli1蛋白表达的阳性细胞百分率均高于对照组（P〈0.05）,Ptch1蛋白表达阳性细胞百分率2组无显著差异（P〉0.05）。结论：RA患者PBMCs与滑膜组织中检测到Shh通路相关信号分子Shh和Gli1的表达上调,提示RA患者中可能存在Shh信号通路的激活,其在RA发病机制中的作用值得进一步研究。

英文摘要：

AIM：To investigate the expression of Sonic Hedgehog（Shh） signaling pathway-associated factors in peripheral blood mononuclear cells（PBMCs） and synovial tissues of rheumatoid arthritis（RA）.METHODS：The mRNA expression levels of Shh,Ptchl and Glil in PBMCs of 35 RA patients,and 35 age-and sex-matched healthy controls were analyzed by real-time PCR.The expression of Shh,Ptchl and Glil in synovial tissues was detected by immunohistochemisty assay in 10 RA patients and 5 patients with traumatic or meniscal injury（no arthritis） as control group.All patients accorded with the American College of Rheumatology（ACR） 1987 revised classification criteria for determining RA,and the score of DAS28 was≥3.2.RESULTS;The results of real-time PCR showed that the expression of Shh and Glil mRNA in RA patients was higher than that in the controls（Shh and Glil in RA were 1.36±1.48 and 1.15±0.68, while Shh and Glil in control group were 0.47±0.25 and 0.49±0.05,respectively）.The mRNA expression of Ptchl between the 2 groups had no significant difference.Similarly,the results of immunohistochemistry assay showed that the positive staining rates of Shh and Glil in RA group were higher than those in control group.However,no difference of Ptchl positive staining rate between the 2 groups was observed（P〉0.05）.CONCLUSION：The positive expression of Shh and Glil indicates the activation of Shh signaling pathway in the RA patients.