Sirtuin-1及SREBP在丙肝进展为肝硬化过程中的变化及临床意义  

Changes and clinical significance of Sirtuin-1 and SREBP in progression of hepatitis C to cirrhosis

作　　者：董金玲 吴天添 谢志宏[1] 张颖[1] DONG Jinling;WU Tiantian;XIE Zhihong;ZHANG Ying(Department of Infectious Diseases,the First People＇s Hospital of Huzhou in Zhejiang Province,Huzhou 313000,China;Department of General Surgery,the First People＇s Hospital of Huzhou in Zhejiang Province,Huzhou 313000,China)

机构地区：[1]浙江省湖州市第一人民医院感染科,浙江湖州313000 [2]浙江省湖州市第一人民医院普外科,浙江湖州313000

出　　处：《中国现代医生》2018年第29期17-22,169,共7页China Modern Doctor

基　　金：浙江省自然科学基金(LY16H160041);浙江省医药卫生科技计划项目(2015KYB382)

摘　　要：目的探讨在丙肝病毒(HCV)感染合并脂肪肝及肝硬化的患者中Sirtuin-1和SREBP的变化及其临床意义。方法选择单纯丙肝患者37例,丙肝合并重度脂肪肝患者34例,丙肝合并肝硬化患者31例,正常志愿者35例,共137例。分别采集各入组者的外周血样本、丙肝合并重度脂肪肝及丙肝后肝硬化患者的肝脏穿刺样本,通过Realtime qPCR及Western Blotting方法检测Sirtuin-1和SREBP的转录和表达水平。结果血液中Sirtuin-1转录水平:与正常人比较,单纯丙肝患者下降(P=0.0013);丙肝合并重度脂肪肝患者又较单纯丙肝患者下降(P=0.0006);而在丙肝后肝硬化与丙肝合并重度脂肪肝患者之间无统计学差异(P=0.2741);但丙肝合并肝硬化患者仍较单纯丙肝患者有明显下降(P=0.0026)。血液中SREBP-1c转录水平:单纯丙肝患者较正常人高(P=0.0130);丙肝合并重度脂肪肝较单纯丙肝患者高(P=0.0021);丙肝后肝硬化较丙肝合并重度脂肪肝患者亦有升高(P=0.0481)。血液中Sirtuin-1表达水平:正常人、单纯丙肝患者、丙肝合并重度脂肪肝患者、丙肝后肝硬化患者逐步下降(P分别为0.0003、0.000021、0.0207)。血液中SREBP-1c表达水平:正常人、单纯丙肝患者、丙肝合并重度脂肪肝患者逐步升高(P分别为0.00017、0.0003),而丙肝合并重度脂肪肝与丙肝后肝硬化患者之间则无明显差异(P=0.0814)。SREBP-2在血液中mRNA及蛋白水平表达均无显著统计学差异(P>0.05)。肝穿组织中:Sirtuin-1基因转录与蛋白表达水平,丙肝后肝硬化患者均较丙肝合并重度脂肪肝患者低(P分别为0.0013和0.0001);而SREBP-1c的基因转录与蛋白表达水平,丙肝后肝硬化患者均较丙肝合并重度脂肪肝患者高(P分别为0.0201和0.0083);SREBP-2转录和表达在两组间无差异(P>0.05)。结论 HCV有可能通过下调Sirtuin-1及上调SREBP-1c的表达加重肝细胞的脂质化及肝硬化的程度。Objective To explore the changes and clinical significance of Sirtuin-1 and SREBP in hepatitis C virus（HCV） infected patients with fatty liver and liver cirrhosis. Methods A total of 137 patients, including 37 patients withHCV alone, 34 patients with HCV with severe fatty liver, 31 patients with HCV and cirrhosis, 35 patients with normalvolunteers, were selected. The peripheral blood samples of the enrolled patients, liver puncture samples from patientswith HCV with severe fatty liver and those with HCV and cirrhosis were collected. Transcription and expression of Sirtuin-1 and SREBP was detected by Realtime qPCR and Western Blotting. Results Compared with that of normal people, the Sirtuin-1 transcription level in blood in patients with hepatitis C decreased（P=0.0013）. The Sirtuin-1 transcription level in patients with HCV and severe fatty liver was lower than that of patients with hepatitis C（P=0.0006）.While there was no significant difference in the Sirtuin-1 transcription level between patients with HCV and severe fattyliver and those with HCV and cirrhosis（P=0.2741）. However, the Sirtuin1 transcription level in patients with hepatitis Cand liver cirrhosis was still significantly lower than that of patients with only hepatitis C（P=0.0026）. SREBP-1c transcription level in blood in hepatitis C patients was higher than that of normal people（P=0.0130）. The SREBP-1c transcription level in patients with HCV and severe fatty liver was higher than that of patients with hepatitis C（P=0.0021）.And SREBP-1c transcription level in patients with HCV and cirrhosis was also higher than that of patients with HCVand severe fatty liver（P=0.0481）. The expression level of Sirtuin1 in blood was gradually decreased in normal subjects,patients with hepatitis C only, patients with hepatitis C and severe fatty liver, and patients with hepatitis C and cirrhosis（P=0.0003, 0.000021, and 0.0207, respectively）. The SREBP-1c expression level in blood was increased gradually innormal subjects, patients wit

关 键 词：Sirtuin-1 SREBP-1C SREBP-2 HCV 肝脂肪变性 肝硬化 

分 类 号：R512.63[医药卫生—内科学]