【作者】 王艳；

【导师】 赵龙凤；

【作者基本信息】 山西医科大学 ， 传染病学， 2004， 硕士

【摘要】 目的探讨慢性HBV感染者(CHB)外周血白介素-2（IL-2）、γ-干扰素（IFN-γ）活性与病毒载量、肝功能状态以及肝纤维化的关系。探讨各临床分型HBV感染者ApoE基因多态性的分布情况，并分析其对慢性HBV感染性免疫的影响。方法测定慢性HBV感染者外周血Th1型细胞因子IL-2、IFN-γ水平，IL-2检测采用放射免疫法（RIA法），IFN-γ检测采用双抗夹心法（ELISA法）。对慢性HBV感染者外周静脉抗凝血进行DNA抽提，PCR扩增ApoE基因片段，用荧光偏振的方法检测ApoE基因型。3、根据病毒载量不同选出低载量组和高载量组；根据病情及肝功能状况分为CHB携带组、轻度组、中度组及重度组；根据有无肝纤维化分为肝硬化组和非肝硬化组；根据ApoE三种基因型不同分为ApoEε2组、ApoEε3组及ApoEε4组。结果1、HBV DNA高载量组与低载量组相比IL-2水平显著低下（P﹤0.05），两组间INF-γ水平无明显差异。随着肝功能损害程度增加IL-2含量逐渐降低，INF-γ逐渐增高；与非肝硬化组比较肝硬化组的IL-2的含量显著降低，IFN-γ显著升高（均P﹤0.01）。2、三种ApoE基因型在慢性HBV感染者中的分布频率ApoEε3：ApoEε4：ApoEε2为0.74：0.16：0.10，与正常人群频率相比无明显差异。轻度组ApoEε4（0.22）高于正常值范围（0.04(0.17），并与中度、重度组相比有显著差异（均P(0.05）；肝硬化组与非肝硬化组之间ApoE基因频率无差异；与ApoEε3、ApoEε2组相比ApoEε4组有较高的IL-2和总胆固醇水平。结论 <WP=5>在乙肝慢性化过程中，IL-2与HBV清除有关，其降低的程度与肝损伤严重程度及肝纤维化相关；IFN-γ的抗病毒作用不明显，但它作为炎症介质参与了肝脏炎症坏死和肝纤维化的形成过程。高水平的ApoEε4基因可通过调节IL-2和血脂水平减轻HBV感染后引起的肝细胞炎症反应，对抗HBV感染后的肝损伤。更多还原

【Abstract】 Objective1. To explore the relationship among IL-2, IFN-γin sera and HBV load , hepatic function condition and liver fibrosis in patients with chronic hepatitis B (CHB).2. To deserve the frequency distribution of ApoE phenotypes and alleles in chronic HBV infected with different clinical manifestations, and the effects of ApoE gene polymorphism in HBV infective immunity were analyzed.Methods1. The quantity of IL-2 and IFN-γin sera were measured, the RIA and ELISA technique were separately used to detect IL-2 and IFN-γ. 2. The blood genome DNA of chronic hepatitis B were extracted, PCR and TDI-FP technique were separately used to copy the ApoE gene and detection of ApoE gene types. 3. According to the virus load the low-quantity group and high-quantity group was choosed out . According to the hepatic function condition the patients was divided into the chronic CHB Virus taking, light-degree, mid-degree and severe-degree group. According to liver fibrosis condition the cirrhosis group and non-cirrhosis group were divided. According to the ApoE gene polymorphism the patients were divided into the ApoEε2 group, ApoEε3 group and ApoEε4 group.Results1. Compared with the low-quantity group the IL-2 in high-quantity group was significantly decreased (P﹤0.05), there was no difference of IFN-γ between them. Along with the severer of hepatic function the IL-2 quantity was decreased and the IFN-γ was increased. Compared with the non-cirrhosis group the IL-2 in cirrhosis group was significantly decreased and the IFN-γwas increased（P﹤0.01）. <WP=7>2. The allele frequencies of ApoE in the chronic hepatitis B ApoEε3: ApoEε4: ApoEε2 were 0.74: 0.16: 0.10, There was no significant difference in the chronic HBV-infected compared with previously published population data, however, the frequency of the ApoEε4 in light-degree(0.22) was higher than the population data（0.04(0.17）,and compared with the CHB mid-degree and severe-degree groups, it was significantly higher (P﹤0.05).The ApoE allele frequencies were similar in cirrhosis group and non-cirrhosis group. Compared with the ApoEε3 and ApoEε2 the IL-2 and TC in ApoEε4 were higher. Conclusions1. The activity of IL-2 shows a beneficial effects on eliminating HBV, the quantity of IL-2 has relationship with liver damage and fibrosis formation. There is no beneficial effects of IFN-γon eliminating HBV, and it can accelerate the liver necrosis and fibrosis formation.2. The high carriage of ApoEε4 allele may lighten the hepatic inflammatory damage through regulate the quantity of IL-2 and plasma lipid levels in sera.更多还原