慢性HBV感染者肝脏组织IL-12表达及其意义
发布时间：2018-11-22 06:47
【摘要】：背景目前慢性HBV感染的免疫发病机制尚不太清楚。急性自限性HBV感染时Th1占优，宿主启动了强有效的、多克隆的、多特异性的免疫反应，，有利于病毒清除和肝功能的恢复。反之，Th2占优时感染者不能产生强有力的免疫反应，不足以及时有效地清除受染肝细胞中的病毒，导致感染的慢性化。IL-12有助于分化调节Th1/Th2平衡，促使Th0细胞向Th1方向分化成熟，阻止Th0向Th2方向的发展，增强细胞毒性T细胞的活性，诱导病毒特异性Th细胞活动的发生，抑制病毒的复制及表达。但IL-12在慢性HBV感染者肝脏组织中的表达及临床意义尚未见报道。 目的探讨细胞因子白细胞介素-12在肝脏组织中表达与HBV感染慢性化发病的相关性，采用SP免疫组化法检测慢性HBV感染相关性肝病患者肝脏组织中IL-12表达，研究IL-12在疾病进展中的可能作用，评估检测慢性HBV感染者肝脏组织IL-12表达强度作为常规免疫标记的可能性。 方法应用半定量SP免疫组化法检测107例慢性乙型肝炎，41例乙肝后肝硬化，37例乙肝后肝癌，76例慢性HBsAg携带者肝脏组织中IL-12的表达情况，另选9个健康人作对照组。采用常规生化方法检测肝功能，采用ELISA法检测HBV血清学标记物，采用荧光定量PCR试剂盒检测HBV-DNA。 结果 1. IL-12主要在肝细胞胞浆中表达。半定量分析结果显示，IL-12在CHB、肝硬化、HBV相关性肝癌组织中的表达水平存在显著差异(P0.05)。 2. CHB患者IL-12表达情况与病理分级的相关性比较，差异无统计学意义(P0.05)。 3. IL-12在肝癌及癌旁组织中的表达情况比较，差异无统计学意义(P0.05)。 4. CHB患者IL-12的表达情况与HBeAg阳性、HBV-DNA等因素比较，差异无统计学意义(P0.05)，CHB患者IL-12的表达情况与ALT水平比较差异显著(P0.05)。 5.肝功能正常的慢性HBV感染者中，HBeAg阳性者IL-12阴性表达率显著高于HBeAg阴性者，HBV-DNA水平高的患者IL-12阴性表达率高，HBV-DNA水平低的患者IL-12阳性表达率高(P0.05)；免疫耐受者IL-12阴性表达率高，低或非复制期者IL-12阳性表达率高(P0.05)。 结论 1. IL-12在CHB、肝硬化、HBV相关性肝癌组织中的表达存在显著差异，提示IL-12与HBV感染的免疫发病机制有关，可能参与HBV感染的慢性化、疾病的进展与转归。 2.不同HBeAg状态及HBV-DNA病毒载量水平的CHB患者肝脏内IL-12的表达差异有统计学意义，提示IL-12可能参与HBeAb的产生及HBV的清除。
[Abstract]:Background at present, the immune pathogenesis of chronic HBV infection is still unclear. In acute self-limited HBV infection, Th1 dominates, and the host initiates a highly effective, polyclonal, multi-heterosexual immune response, which is conducive to virus clearance and liver function recovery. On the other hand, when Th2 is dominant, the infected person can not produce a strong immune response, which is not sufficient to remove the virus in the infected liver cells in time and effectively, leading to the chronic infection. IL-12 helps to differentiate and regulate the balance of Th1/Th2. Th0 cells were induced to differentiate and mature towards Th1, to prevent the development of Th0 towards Th2, to enhance the activity of cytotoxic T cells, to induce the activity of virus-specific Th cells, and to inhibit the replication and expression of viruses. However, the expression and clinical significance of IL-12 in the liver tissues of patients with chronic HBV infection have not been reported. Objective to investigate the relationship between the expression of cytokine interleukin-12 (IL-12) in liver tissue and the pathogenesis of chronic HBV infection, and to detect the expression of IL-12 in liver tissue of patients with chronic HBV infection associated liver disease by SP immunohistochemical method. To study the possible role of IL-12 in the progression of the disease and to evaluate the possibility of detecting the expression of IL-12 in liver tissue of chronic HBV infected patients as a routine immunological marker. Methods the expression of IL-12 in the liver tissues of 107 cases of chronic hepatitis B, 41 cases of posthepatitic cirrhosis, 37 cases of liver cancer after hepatitis B and 76 cases of chronic HBsAg carriers were detected by semi-quantitative SP immunohistochemical method. Routine biochemical method was used to detect liver function, ELISA method was used to detect HBV serological marker, and fluorescent quantitative PCR kit was used to detect HBV-DNA.. Result 1. IL-12 is mainly expressed in the cytoplasm of hepatocytes. The results of semi-quantitative analysis showed that there was significant difference in the expression of IL-12 in CHB, cirrhosis and HBV related liver cancer (P0.05). 2. There was no significant difference between the expression of IL-12 and pathological grade in CHB patients (P0.05). 3. There was no significant difference in the expression of IL-12 in liver cancer and adjacent tissues (P0.05). 4. There was no significant difference between the expression of IL-12 and HBeAg and HBV-DNA in CHB patients (P0.05). The expression of IL-12 in), CHB patients was significantly higher than that in ALT (P0.05). 5. In patients with chronic HBV infection with normal liver function, the negative expression rate of IL-12 in HBeAg positive patients was significantly higher than that in HBeAg negative patients, and IL-12 negative expression rate was higher in patients with high HBV-DNA level. The positive expression rate of IL-12 in patients with low HBV-DNA level was high (P0.05). The negative expression rate of IL-12 was high in immune tolerance group, and the positive rate of IL-12 was high in low or non replicating stage (P0.05). Conclusion 1. There were significant differences in the expression of IL-12 in CHB, cirrhosis and HBV associated liver cancer tissues, suggesting that IL-12 is related to the immune pathogenesis of HBV infection, and may be involved in the chronicity of HBV infection and the progression and outcome of HBV infection. 2. There were significant differences in the expression of IL-12 in the liver of CHB patients with different HBeAg status and HBV-DNA viral load, suggesting that IL-12 might be involved in the production of HBeAb and the clearance of HBV.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R512.62
本文编号：2348403
[Abstract]:Background at present, the immune pathogenesis of chronic HBV infection is still unclear. In acute self-limited HBV infection, Th1 dominates, and the host initiates a highly effective, polyclonal, multi-heterosexual immune response, which is conducive to virus clearance and liver function recovery. On the other hand, when Th2 is dominant, the infected person can not produce a strong immune response, which is not sufficient to remove the virus in the infected liver cells in time and effectively, leading to the chronic infection. IL-12 helps to differentiate and regulate the balance of Th1/Th2. Th0 cells were induced to differentiate and mature towards Th1, to prevent the development of Th0 towards Th2, to enhance the activity of cytotoxic T cells, to induce the activity of virus-specific Th cells, and to inhibit the replication and expression of viruses. However, the expression and clinical significance of IL-12 in the liver tissues of patients with chronic HBV infection have not been reported. Objective to investigate the relationship between the expression of cytokine interleukin-12 (IL-12) in liver tissue and the pathogenesis of chronic HBV infection, and to detect the expression of IL-12 in liver tissue of patients with chronic HBV infection associated liver disease by SP immunohistochemical method. To study the possible role of IL-12 in the progression of the disease and to evaluate the possibility of detecting the expression of IL-12 in liver tissue of chronic HBV infected patients as a routine immunological marker. Methods the expression of IL-12 in the liver tissues of 107 cases of chronic hepatitis B, 41 cases of posthepatitic cirrhosis, 37 cases of liver cancer after hepatitis B and 76 cases of chronic HBsAg carriers were detected by semi-quantitative SP immunohistochemical method. Routine biochemical method was used to detect liver function, ELISA method was used to detect HBV serological marker, and fluorescent quantitative PCR kit was used to detect HBV-DNA.. Result 1. IL-12 is mainly expressed in the cytoplasm of hepatocytes. The results of semi-quantitative analysis showed that there was significant difference in the expression of IL-12 in CHB, cirrhosis and HBV related liver cancer (P0.05). 2. There was no significant difference between the expression of IL-12 and pathological grade in CHB patients (P0.05). 3. There was no significant difference in the expression of IL-12 in liver cancer and adjacent tissues (P0.05). 4. There was no significant difference between the expression of IL-12 and HBeAg and HBV-DNA in CHB patients (P0.05). The expression of IL-12 in), CHB patients was significantly higher than that in ALT (P0.05). 5. In patients with chronic HBV infection with normal liver function, the negative expression rate of IL-12 in HBeAg positive patients was significantly higher than that in HBeAg negative patients, and IL-12 negative expression rate was higher in patients with high HBV-DNA level. The positive expression rate of IL-12 in patients with low HBV-DNA level was high (P0.05). The negative expression rate of IL-12 was high in immune tolerance group, and the positive rate of IL-12 was high in low or non replicating stage (P0.05). Conclusion 1. There were significant differences in the expression of IL-12 in CHB, cirrhosis and HBV associated liver cancer tissues, suggesting that IL-12 is related to the immune pathogenesis of HBV infection, and may be involved in the chronicity of HBV infection and the progression and outcome of HBV infection. 2. There were significant differences in the expression of IL-12 in the liver of CHB patients with different HBeAg status and HBV-DNA viral load, suggesting that IL-12 might be involved in the production of HBeAb and the clearance of HBV.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R512.62
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