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目的通过研究原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)患者外周血单个核细胞(peripheral blood mononuclear cells,PBMC)中免疫球蛋白G Fc段受体Ⅲa(Fc fragment of IgG,low affinity Ⅲ a,receptor,FCGR3A)和酪氨酸激酶结合蛋白(tyrosine kinase binding protein,TYROBP)mRNA的表达,探讨FCGR3A和TYROBP在PBC发病机制中的作用及临床意义。方法采用实时荧光定量逆转录(FQ-RT)-PCR检测80例PBC、55例慢性乙型肝炎(chronic hepatitis type B,CHB)和68名健康对照者(healthy control,HC)PBMC中FCGR3A和TYROBP mRNA基因表达水平,以2-△△Ct法计算基因表达的量,并比较FCGR3A mRNA与TYROBP mRNA表达水平的相关性及FCGR3A和TYROBP mRNA表达水平与肝功能指标的相关性。结果 PBC患者PBMC中FCGR3A mRNA表达水平(1.96±1.87)显著高于疾病对照组CHB患者(1.38±1.19,P=0.044)和HC组(0.75±0.40,P=0.000),CHB患者也明显高于HC组(P=0.000);PBC患者PBMC中TYROBP mRNA表达水平(1.29±0.66)显著高于HC组(0.98±0.36,P=0.009),而与CHB患者无明显差异(1.19±0.76,P=0.233);PBC患者FCGR3A与TYROBP mRNA表达水平有显著相关性(r=0.519,P=0.000);FCGR3A mRNA表达水平与PBC患者肝功能指标r-谷氨酰转肽酶(GGT)的含量呈明显正相关(r=0.427,P=0.000),而与其他指标无相关;PBC患者TYRBOP mRNA表达水平与肝功能指标无相关。结论 PBC患者FCGR3A和TYROBP mRNA表达水平的异常,表明FCGR3A和TYROBP可能参与PBC的发病和疾病的维持。FCGR3A mRNA的表达和肝功能指标GGT相关,可能直接参与PBC肝损伤。
OBJECTIVE: To study the effect of Fc fragment of IgG (Ⅲ) on the expression of low affinity Ⅲ (Fc) of peripheral blood mononuclear cells (PBMC) in patients with primary biliary cirrhosis (PBC) a, receptor, FCGR3A) and tyrosine kinase binding protein (TYROBP) mRNA, to explore the role of FCGR3A and TYROBP in the pathogenesis of PBC and its clinical significance. Methods FQ-RT-PCR was used to detect the expression of FCGR3A and TYROBP in 80 cases of PBC, 55 cases of chronic hepatitis B (CHB) and 68 healthy controls (HC) The gene expression levels were calculated by 2- △△ Ct method. The correlation between FCGR3A mRNA expression and TYROBP mRNA expression and the correlation between FCGR3A and TYROBP mRNA expression and liver function were compared. Results The level of FCGR3A mRNA in PBMC from PBC patients (1.96 ± 1.87) was significantly higher than that in CHB patients (1.38 ± 1.19, P = 0.044) and HC group (0.75 ± 0.40, P = 0.000) (P = 0.000). The expression level of TYROBP mRNA in PBMC of PBC patients (1.29 ± 0.66) was significantly higher than that of HC patients (0.98 ± 0.36, P = 0.009), but no significant difference with CHB patients (1.19 ± 0.76, P = 0.233). There was a significant correlation between the expression of FCGR3A and TYROBP mRNA in PBC patients (r = 0.519, P = 0.000). The expression of FCGR3A mRNA and GGT in patients with PBC were significantly increased (R = 0.427, P = 0.000), but no correlation with other indexes. The expression of TYRBOP mRNA in PBC patients was not correlated with liver function. Conclusions The abnormal expression of FCGR3A and TYROBP mRNA in PBC patients suggests that FCGR3A and TYROBP may be involved in the pathogenesis and maintenance of PBC. The expression of FCGR3A mRNA correlates with GGT, which may play a direct role in PBC liver injury.