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慢性丙型肝炎患者外周血Toll样受体3和7与Ⅰ型干扰素基因表达的研究

mRNA expressions of Toll-like receptor 3, 7 and type Ⅰ interferons in peripheral blood of patients with chronic hepatitis C

摘要目的 观察慢性丙型肝炎(CHC)患者外周血单个核细胞(Peripheral blood mononuclear cells,PBMC)中Toll样受体3(Toll like receptor 3,TLR3)和7(TLR7),以及Ⅰ型干扰素α(Interferonα,IFN-α)和β(IFN-β) mRNA的表达,探寻CHC治疗的新方法.方法 选择2013年9月至2014年5月武汉大学人民医院收治住院的30例CHC患者,并选择同期体检的健康人群30名作为健康对照组.采用酶联免疫吸附试验(ELISA)检测肝功能指标;用实时荧光定量PCR检测TLR3、TLR7、IFN-α和IFN-β mRNA表达,并用2-△△Ct方法计算相对表达量.两样本均数比较采用t检验,TLR mRNA与IFNmRNA表达、肝功能指标及HCV RNA载量之间的相关性采用Pearson相关性分析.结果 健康对照组的基因表达量为1,CHC组TLR3、TLR7、IFN-α和IFN-β mRNA的相对表达量分别为0.086、0.633、0.145和0.423,两组间比较差异均有统计学意义(=4.25,2.39,2.37和2.80,P值均<0.01).Pearson相关性分析显示,TLR3和TLR7 mRNA表达量与IFN-β mRNA表达量呈正相关性(r=0.381和0.487,P值均<0.05),但与IFN-α mRNA表达量、HCV RNA载量、丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平无相关性(P值均>0.05).结论 CHC患者TLR3、TLR7mRNA以及IFN-α、IFN-β mRNA表达均降低,且TLR3和TLR7mRNA表达与IFN-β mRNA呈正相关,提示可通过提高TLR受体的表达为CHC的治疗提供新的方法.

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abstractsObjective To investigate mRNA expressions of Toll-like receptors (TLR3 and TLR7)and type Ⅰ interferons (IFN-α and IFN-β) in peripheral blood mononuclear cells (PBMCs) of patients with chronic hepatitis C (CHC).Methods Thirty patients with CHC and 30 healthy controls were collected from Renmin Hospital of Wuhan University during September 2013 and May 2014.Liver function was detected using enzyme-linked immunosorbent assay (ELISA).mRNA expressions of TLR3,TLR7,IFN-α and IFN-β were detected by real-time quantitative PCR,and their relative expression values were obtained by 2-△△Ctmethod.The t test was performed for the comparison of mean differences between CHC patients and healthy controls,and Pearson analysis was used to analyze the correlations between TLR mRNA and IFN mRNA,liver function,HCV RNA load.Results Taking mRNA expressions in healthy control group as 1,the relative mRNA expressions of TLR3,TLR7,IFN-α and IFN-β in CHC group were 0.086,0.633,0.145 and 0.423 respectively (t =4.25,2.39,2.37 and 2.80,all P < 0.01).Pearson correlation analysis showed that mRNA expressions of TLR3 and TLR7 were positively correlated with that of IFN-β (r =0.381 and 0.487,all P < 0.05),but not correlated with IFN-α mRNA expression,HCV RNA load,ALT and AST (all P > 0.05).Conclusion The mRNA expressions of TLR3,TLR7 and IFN-α,IFN-β decrease in CHC patients,and the mRNA expressions of TLR3 and TLR7 are positively correlated with that of IFN-β,indicating that increasing the expression of TLRs might be a new strategy in CHC treatment.

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