PBMC组蛋白乙酰化在强直性脊柱炎中的作用

The effect of histone acetylation in PBMC on pathogenesis of ankylosing spondylitis

为研究强直性脊柱炎(ankylosing spondylitis, AS)患者PBMC组蛋白乙酰化水平,探究其在AS发病中的作用,收集32例AS稳定组患者、26例AS活动组患者和25例正常对照者的静脉血,采用H3/H4乙酰化检测试剂盒检测PBMC组蛋白H3、H4乙酰化水平,RT-PCR检测AS患者PBMC组蛋白乙酰基转移酶(histone acetyltransferase,HAT)和去乙酰基转移酶(histone deacetylase,HDAC)基因的mRNA表达水平。与正常对照组比较,AS活动组和AS稳定组患者PBMC组蛋白H3、H4均呈低乙酰化水平(P <0.05);AS活动组和AS稳定组患者PBMC的P300、CREBBP和HDAC2 mRNA表达水平均明显降低(P <0.05)。AS患者PBMC组蛋白H3、H4乙酰化水平与AS疾病活动度指数(ASDAS)呈正相关(P <0.05)。AS患者PBMC组蛋白乙酰化异常,且与AS的发生、发展有一定相关性。

To study the histone acetylation patterns in PBMC from ankylosing spondylitis (AS) patients, 32 patients with stable AS (stable group), 26 patients with active AS (active group) and 25 healthy controls were recruited.The PBMC were isolated and global H3/H4 acetylation was determined by assay kit.The differential expressions of the histone acetyltransferases(HAT) and the histone deacetylases(HDAC) were measured by RT-PCR.Decreased global H3/H4 acetylation was observed in PBMCs from AS patients of active group and stable group compared with that of the healthy controls (P<0.05). The mRNA levels of gene P300,CREBBP and HDAC2 in AS patients of both active group and stable group were decreased,compared with healthy controls(P<0.05).In AS patients, global histone H3/H4 acetylation was significantly positively correlated with ASDAS (P<0.05).Thus, histone acetylation appears abnormal in PBMCs of AS patients,which may be related to the pathogenesis of AS.