【摘要】：背景目前慢性HBV感染的免疫發(fā)病機制尚不太清楚。急性自限性HBV感染時Th1占優(yōu)，宿主啟動了強有效的、多克隆的、多特異性的免疫反應(yīng)，，有利于病毒清除和肝功能的恢復(fù)。反之，Th2占優(yōu)時感染者不能產(chǎn)生強有力的免疫反應(yīng)，不足以及時有效地清除受染肝細胞中的病毒，導(dǎo)致感染的慢性化。IL-12有助于分化調(diào)節(jié)Th1/Th2平衡，促使Th0細胞向Th1方向分化成熟，阻止Th0向Th2方向的發(fā)展，增強細胞毒性T細胞的活性，誘導(dǎo)病毒特異性Th細胞活動的發(fā)生，抑制病毒的復(fù)制及表達。但IL-12在慢性HBV感染者肝臟組織中的表達及臨床意義尚未見報道。 目的探討細胞因子白細胞介素-12在肝臟組織中表達與HBV感染慢性化發(fā)病的相關(guān)性，采用SP免疫組化法檢測慢性HBV感染相關(guān)性肝病患者肝臟組織中IL-12表達，研究IL-12在疾病進展中的可能作用，評估檢測慢性HBV感染者肝臟組織IL-12表達強度作為常規(guī)免疫標記的可能性。 方法應(yīng)用半定量SP免疫組化法檢測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攜帶者肝臟組織中IL-12的表達情況，另選9個健康人作對照組。采用常規(guī)生化方法檢測肝功能，采用ELISA法檢測HBV血清學(xué)標記物，采用熒光定量PCR試劑盒檢測HBV-DNA。 結(jié)果 1. IL-12主要在肝細胞胞漿中表達。半定量分析結(jié)果顯示，IL-12在CHB、肝硬化、HBV相關(guān)性肝癌組織中的表達水平存在顯著差異(P0.05)。 2. CHB患者IL-12表達情況與病理分級的相關(guān)性比較，差異無統(tǒng)計學(xué)意義(P0.05)。 3. IL-12在肝癌及癌旁組織中的表達情況比較，差異無統(tǒng)計學(xué)意義(P0.05)。 4. CHB患者IL-12的表達情況與HBeAg陽性、HBV-DNA等因素比較，差異無統(tǒng)計學(xué)意義(P0.05)，CHB患者IL-12的表達情況與ALT水平比較差異顯著(P0.05)。 5.肝功能正常的慢性HBV感染者中，HBeAg陽性者IL-12陰性表達率顯著高于HBeAg陰性者，HBV-DNA水平高的患者IL-12陰性表達率高，HBV-DNA水平低的患者IL-12陽性表達率高(P0.05)；免疫耐受者IL-12陰性表達率高，低或非復(fù)制期者IL-12陽性表達率高(P0.05)。 結(jié)論 1. IL-12在CHB、肝硬化、HBV相關(guān)性肝癌組織中的表達存在顯著差異，提示IL-12與HBV感染的免疫發(fā)病機制有關(guān)，可能參與HBV感染的慢性化、疾病的進展與轉(zhuǎn)歸。 2.不同HBeAg狀態(tài)及HBV-DNA病毒載量水平的CHB患者肝臟內(nèi)IL-12的表達差異有統(tǒng)計學(xué)意義，提示IL-12可能參與HBeAb的產(chǎn)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.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R512.62

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