【摘要】 目的探讨ASC与Caspase-1在原发性胆汁性肝硬化(PBC)发病过程中的影响。方法采用实时荧光定量PCR、Western blot、焦磷酸测序及ELISA等方法分别检测30例PBC患者及健康对照者外周血单个核细胞(PBMC)中Caspase-1与ASC的mRNA和蛋白的相对表达情况,以及ASC启动子区甲基化状况和血浆中Caspase-1和IL-18的表达水平。结果 PBC组患者PBMC中Caspase-1、ASC mRNA和蛋白表达明显高于对照组(P<0.05)。ASC启动子区域Island 1(IS1)各位点甲基化率明显低于对照组(P<0.05),Island 2(IS2)各位点甲基化率小于背景值,未发生甲基化。PBC组血浆中Caspase-1与IL-18的水平明显高于对照组(P<0.05)。ASC mRNA与Caspase-1mRNA的表达呈明显正相关(P<0.05);ASC启动子区域IS1的第1、2、4和5位点的甲基化率与ASC mRNA的表达均呈负相关(P<0.05),第3、6位点甲基化率则与其表达无相关性(P>0.05);血浆中Caspase-1与IL-18水平呈明显正相关(P<0.05)。结论 ASC和Caspase-1参与了PBC的免疫炎性反应。更多还原

【Abstract】 Objective To explore the influence of apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC)and Caspase-1 on the pathogenesis of primary biliary cirrhosis(PBC).Methods The real-time PCR,Western blot,pyrophosphate sequencing and ELISA were adopted to respectively detect the relative expressions of mRNA and protein of peripheral blood mononuclear cells(PBMS)Caspase-1 and ASC as well as the methylation status of ASC promoter region and plasma Caspase-1 and IL-18 expression levels in 30 cases of PBC and healthy controls.Results The mRNA and protein expressions of PBMC Caspase-1 and ASC in the PBC group were significantly higher than those in the control group(P<0.05).The methylation rate of ASC promoter Island1(ISI)was significantly lower than that of the control group(P<0.05),which of Island 2(IS2)was smaller than the background value and had no methylation occurrence.The levels of plasma Caspase-1 and IL-18 in the PBC group were significantly higher than those in the control group(P<0.05).The ASC mRNA in the PBC group was significantly correlated with the Caspase-1 mRNA expression(P<0.05);the methylation rates at loci 1,2,4,5 of ASC promoter region CpG island were negatively correlated with ASC mRNA expression(P<0.05),and which at loci 3,6 had no correlation with their expressions(P>0.05);plasma Caspase-1 and IL-18 levels showed the obviously positive correlation.Conclusion ASC and Caspase-1 are involved in the immune inflammatory response in PBC.更多还原