發(fā)布時間：2018-12-26 15:21

【摘要】：目的：通過比較廣西南寧,柳州,桂林三地人群肝癌組織和正常肝組織中hOGG1修復(fù)蛋白和MGMT修復(fù)蛋白的表達(dá)水平,了解三地人群肝組織中DNA損傷的修復(fù)情況及其AFB1暴露的關(guān)系。 材料和方法：收集南寧,柳州,桂林三地病理蠟塊切片共428例,其中南寧地區(qū)HCC組103例,正常對照組58例；柳州地區(qū)HCC組89例,正常對照組55例；桂林地區(qū)HCC組86例,正常對照組37例。通過免疫組織化學(xué)(Immunohistochemistry, IHC)法檢測hOGG1蛋白,MGMT修復(fù)蛋白表達(dá)水平及AFB1-DNA加合物水平的表達(dá)情況。 結(jié)果：三地HCC組的hOGG1蛋白表達(dá)水平和平均光密度值均高于正常對照組(P0.05)。三地HCC組中,南寧HCC組表達(dá)水平和平均光密度值最高(P0.05)。三地正常對照組的hOGG1蛋白表達(dá)水平和平均光密度值也存在差異(P0.05),南寧正常對照組表達(dá)水平和平均光密度值最高,桂林正常對照組表達(dá)水平和平均光密度值最低；三地HCC組的MGMT蛋白表達(dá)水平和平均光密度值均低于正常對照組(P0.05)；三地HCC組的MGMT蛋白表達(dá)水平和平均光密度值無顯著差異(P0.05),三地正常對照組的MGMT蛋白表達(dá)水平和平均光密度值無顯著差異(P0.05)；南寧HCC組AFB1-DNA加合物陽性表達(dá)水平和平均光密度高于癌旁組(P0.05)和正常對照組(P0.05),柳州HCC組AFB1-DNA加合物陽性表達(dá)水平和平均光密度高于正常對照組(P0.05),桂林地區(qū)AFB1-DNA加合物陽性表達(dá)水平和平均光密度與正常對照組無差異(P0.05)。三地HCC組中,南寧組表達(dá)水平和平均光密度最高(P0.05),桂林組表達(dá)水平和平均光密度最低。三地正常對照組陽性表達(dá)水平無明顯差異(P0.05)。hOGG1修復(fù)蛋白表達(dá)與AFB1-DNA加合物表達(dá)在南寧地區(qū)的HCC組、癌旁組和正常對照組的均存在相關(guān)性,而在柳州和桂林地區(qū)各組中未發(fā)現(xiàn)有明顯相關(guān)性。MGMT修復(fù)蛋白表達(dá)與AFB1-DNA加合物表達(dá)在三地各組中均未發(fā)現(xiàn)有明顯相關(guān)性。 結(jié)論：三地肝癌人群中肝細(xì)胞DNA氧化損傷修復(fù)水平存在差異,MGMT修復(fù)蛋白表達(dá)缺失造成DNA損傷修復(fù)功能下降可能在肝癌的發(fā)生過程中起到重要作用。廣西AFB1暴露水平存在區(qū)域性分布差異,南寧地區(qū)AFB1暴露水平要高于以桂林地區(qū)。AFB1暴露是HCC高發(fā)的危險因素。同時在較高的AFB1暴露水平下,氧化損傷修復(fù)蛋白hOGG1表達(dá)與AFB1-DNA加合物表達(dá)呈現(xiàn)相關(guān)性相關(guān),嚴(yán)重的DNA氧化損傷可能為AFB1致肝癌的重要原因之一。
[Abstract]:Objective: to compare the expression levels of hOGG1 repair protein and MGMT repair protein in liver cancer tissues and normal liver tissues in Nanning, Liuzhou and Guilin, Guangxi, and to understand the repair of DNA damage and the relationship between AFB1 exposure and DNA repair in the liver tissues of the three populations. Materials and methods: a total of 428 cases of paraffin sections in Nanning, Liuzhou and Guilin were collected, including 103 cases in HCC group and 58 cases in normal control group in Nanning, 89 cases in HCC group and 55 cases in normal control group in Liuzhou area. There were 86 cases in HCC group and 37 cases in normal control group in Guilin area. The expression of hOGG1 protein, MGMT repair protein and AFB1-DNA adduct were detected by immunohistochemical (Immunohistochemistry, IHC) method. Results: the expression of hOGG1 protein and the average optical density in HCC group were higher than those in normal control group (P0.05). Among the three HCC groups, Nanning HCC group had the highest expression level and average optical density (P0.05). The expression level and average optical density of hOGG1 protein in normal control group were the highest in Nanning control group and the lowest in Guilin normal control group. The expression level and average optical density of MGMT protein in HCC group were lower than those in normal control group (P0.05). There was no significant difference in the expression level and average optical density of MGMT protein in the three HCC groups (P0.05), but there was no significant difference in the MGMT protein expression level and the average optical density value in the normal control group (P0.05). The positive expression level and average optical density of AFB1-DNA adducts in Nanning HCC group were higher than those in paracancerous group (P0.05) and normal control group (P0.05). The positive expression level and average optical density of AFB1-DNA adduct in Liuzhou HCC group were higher than those in normal control group (P0.05), but the positive expression level and average optical density of AFB1-DNA adduct in Guilin area had no difference from those in normal control group (P0.05). Among the three HCC groups, Nanning group had the highest expression level and average optical density (P0.05), and Guilin group had the lowest expression level and mean optical density. The expression of hOGG1 repair protein was correlated with the expression of AFB1-DNA adducts in HCC group, paracancerous group and normal control group in Nanning area. There was no significant correlation between the expression of MGMT repair protein and the expression of AFB1-DNA adduct in Liuzhou and Guilin. Conclusion: there are differences in the repair level of DNA oxidative damage in hepatoma cells in the three regions. The decrease of DNA damage and repair function caused by the loss of MGMT repair protein may play an important role in the pathogenesis of HCC. There were regional distribution differences in AFB1 exposure level in Guangxi, and the AFB1 exposure level in Nanning was higher than that in Guilin. AFB1 exposure was the risk factor of high incidence of HCC. At the same time, the expression of oxidative damage repair protein (hOGG1) was correlated with the expression of AFB1-DNA adducts at high AFB1 exposure level. Severe DNA oxidative damage may be one of the important causes of AFB1 induced liver cancer.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2011
【分類號】：R329

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