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目的探讨人乙肝相关肝硬化和肝卵圆细胞(HPC)分子调控机制差异性。方法选取2012年1月至2014年12月深圳市龙岗区第二人民医院收治的78例乙型肝炎相关肝硬化患者,肝硬化程度:轻度20例,中度33例,重度25例;肝癌患者67例。另外,选择同期于该院体检的15例健康体检者作为对照组。利用实时荧光定量PCR法筛选和检测HPC细胞中靶基因表达水平;采用免疫组化法检测乙型肝炎相关肝硬化患者的HPC细胞数目变化情况及相关蛋白表达水平。结果通过检测发现,表征肿瘤发生的靶基因,如皮细胞粘附分子(Ep CAM)、重组人S100钙结合蛋白A4(S100A4)、基质金属蛋白酶2(MMP-2)、波形蛋白(Vimentin)及转化生长因子-β(TGF-β1)随着乙型肝炎相关肝硬化疾病的严重程度增加而表达增加;免疫组化结果显示,HPC阳性细胞数目随着乙型肝炎相关肝硬化疾病严重程度增加而增加;同时表征潜在肿瘤化的标记蛋白,如NCAM、S100A4以及MMP-2在重度肝硬化患者中也显著增加。结论本研究证明乙型肝炎相关肝硬化的HPC具有转变为肝癌肿瘤干细胞的潜在风险,为乙型肝炎相关肝硬化和肝癌的治疗提供了新的潜在药物靶点和治疗策略。
Objective To investigate the molecular mechanism of molecular regulation of human hepatic cirrhosis and hepatic oval cell (HPC). Methods From January 2012 to December 2014, 78 cases of hepatitis B-related cirrhosis were treated in Second People’s Hospital of Longgang District, Shenzhen. The degree of liver cirrhosis was 20 mild, 33 moderate and 25 severe, 67 patients. In addition, select the same period in the hospital physical examination of 15 cases of healthy people as a control group. The expression level of target genes in HPC cells was screened and detected by real-time fluorescence quantitative PCR. The number of HPC cells and the expression of related proteins in patients with hepatitis B-related cirrhosis were detected by immunohistochemistry. Results The target genes for tumorigenesis were identified as Ep CAM, S100A4, MMP-2, Vimentin and The expression of transforming growth factor-β (TGF-β1) increased with the severity of hepatitis B-related cirrhosis. Immunohistochemistry showed that the number of HPC positive cells increased with the severity of hepatitis B-related cirrhosis Increased; at the same time characterization of potentially tumorigenic marker proteins such as NCAM, S100A4 and MMP-2 also significantly increased in patients with severe cirrhosis. Conclusions This study demonstrates that HPC associated with hepatitis B has potential risk of transforming into hepatocellular cancer stem cells and provides new potential drug targets and treatment strategies for the treatment of hepatitis B related liver cirrhosis and liver cancer.