慢性HBV感染者外周血白细胞GRP78、CHOP和XBP1 mRNA水平变化*

doi:10.3969/j.issn.1672-5069.2015.02.008

实用肝脏病杂志 ›› 2015, Vol. 18 ›› Issue (2): 136-140.doi: 10.3969/j.issn.1672-5069.2015.02.008

慢性HBV感染者外周血白细胞GRP78、CHOP和XBP1 mRNA水平变化^*

潘高峰, 郜玉峰, 叶娇娇, 姜同翠, 沈玉君, 沈玉先

230601 合肥市安徽医科大学第二附属医院肝病科（潘高峰,郜玉峰,叶娇娇）; 基础医学院（姜同翠,沈玉君,沈玉先）

收稿日期:2014-09-18 出版日期:2015-03-10 发布日期:2016-02-19
通讯作者: 郜玉峰,E-mail： aygyf@126.com
作者简介:潘高峰,男,27岁,硕士研究生。主要从事肝病防治研究。E-mail：pgflhd@163.com
基金资助:
安徽省教育厅自然科学基金资助项目（编号： KJ2014A107）

Peripheral leukocyte GRP78,CHOP and XBP1 mRNA levels in patients with chronic hepatitis B viral infection

Pan Gaofeng, Gao Yufeng, Ye Jiaojiao, et al.

Department of Liver Diseases,Secend Hospital Affiliated to Anhui Medical University,Hefei 230601,Anhui Province,China

Received:2014-09-18 Online:2015-03-10 Published:2016-02-19

摘要/Abstract

摘要： 目的探讨慢性HBV感染者外周血白细胞内质网应激相关基因糖调节蛋白78（GRP78）、CCAAT增强子结合蛋白同源蛋白（CHOP）和X盒结合蛋白l（XBP1）mRNA水平及其与临床指标的相关性。方法采用实时荧光定量PCR技术检测40例正常人（NC）、43例慢性无症状HBV携带者（ASC）、47例慢性乙型肝炎（CHB）、41例乙型肝炎肝硬化（LC）和35例乙型肝炎相关肝细胞癌（HCC）患者外周血白细胞GRP78、CHOP和XBP1 mRNA水平,分析其与病毒学和生化学指标的相关性。结果 ASC、CHB、LC和HCC患者外周血白细胞GRP78 mRNA水平和XBP1 mRNA水平分别为（0.58±0.53）和（0.76±0.57）、（0.59±0.67）和（0.50±0.64）、（1.07±1.09）和（1.44±1.00）和（1.17±1.69）和（0.90±1.33）,均显著高于健康人[分别为（0.01±0.61）和（0.01±0.97）,P<0.01和P<0.05];在HBsAg<1500IU/ml、1500~20000IU/ml和>20000IU/ml组患者,GRP78 mRNA水平分别为（0.48±0.59）、（0.76±0.56）和（0.74±0.56）,三组间差异有统计学意义（P<0.05）;HBV DNA水平为1×10³~10⁵copies/ml组XBP1 mRNA水平为（0.86±1.13）,显著低于HBV DNA>1×10⁵copies/ml组[（1.44±1.31）,P<0.05];在不同转氨酶水平间、HBeAg阳性与阴性组间和胆红素正常与升高组间,以上三种基因 mRNA 水平差异均无统计学意义（P>0.05）。结论内质网应激可能与慢性HBV感染后的疾病进展相关。

关键词: 慢性乙型肝炎, 糖调节蛋白78, CCAAT增强子结合蛋白同源蛋白, X盒结合蛋白l, 内质网应激

Abstract: Objective To investigate the changes of glucose regulated protein 78（GRP78）,a endoplasmic reticulum stress （ERS） related gene,C/ enhancer-binding protein homologous protein （CHOP） and X-box binding protein（XBP） 1 mRNA in peripheral leukocytes in patients with chronic hepatitis B viral infections. Methods The mRNA levels in peripheral leukocytes were measured by real time PCR in 43 individuals with asymptomatic hepatitis B virus carriers,47 patients with chronic hepatitis B,41 with hepatitis B related liver cirrhosis,35 with hepatitis B related hepatocellular carcinoma（HCC） and 40 normal healthy persons. Results The GRP78 mRNA levels in hepatitis B virus carriers,in patients with chronic hepatitis B,liver cirrhosis and hepatocellular carcinoma were higher than that in healthy controls[（0.58±0.53）,（0.76±0.57）,（0.59±0.67） and （0.50±0.64） vs. （0.01±0.61）,P<0.01 for all];the XBP 1 mRNA in hepatitis B virus carriers,in patients with chronic hepatitis B,liver cirrhosis and hepatocellular carcinoma were also higher than that in health controls [（1.07±1.09）,（1.44±1.00）,（1.17±1.69） and （0.90±1.33） vs. （0.01±0.97）,P<0.05 for all];The GRP78 mRNA （0.48±0.59） in patients with serum HBsAg levels of <1500 IU/ml were much lower than in with serum 1500~20000 IU/ml[（0.76±0.56）,P<0.05] or >20000 IU/ml[（0.74±0.56）,P<0.05];The XBP 1 mRNA levels in patients with serum HBV DNA levels of 1×10³ to 10⁵copies/ml was lower than in patients with higher serum HBV DNA load（>1×10⁵copies/ml）[（0.86±1.13） vs. （1.44±1.31）,P<0.05];However,there existed no statistical differences as respect to the three mRNA levels among patients with different serum alanine aminotransferase,nor between patients with normal or abnormal serum bilirubin,nor between HBeAg-positive and HBeAg-negative patients. Conclusion Endoplasmic reticulum stress may beassociated with the disease progression in patients with chronic HBV infection.

Key words: Hepatitis B, Glucose regulated protein 78, C/enhancer-binding protein homologous protein, X-box binding protein 1, Endoplasmic reticulum stress

潘高峰, 郜玉峰, 叶娇娇, 姜同翠, 沈玉君, 沈玉先. 慢性HBV感染者外周血白细胞GRP78、CHOP和XBP1 mRNA水平变化^*[J]. 实用肝脏病杂志, 2015, 18(2): 136-140.

Pan Gaofeng, Gao Yufeng, Ye Jiaojiao, et al.. Peripheral leukocyte GRP78,CHOP and XBP1 mRNA levels in patients with chronic hepatitis B viral infection[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2015, 18(2): 136-140.

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慢性HBV感染者外周血白细胞GRP78、CHOP和XBP1 mRNA水平变化^*

Peripheral leukocyte GRP78,CHOP and XBP1 mRNA levels in patients with chronic hepatitis B viral infection

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