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 m RNA levels in patients with chronic hepatitis B viral infection

作　　者：潘高峰[1] 郜玉峰[1] 叶娇娇 姜同翠[2] 沈玉君[2] 沈玉先[2] 

机构地区：[1]安徽医科大学第二附属医院肝病科,合肥市230601 [2]安徽医科大学第二附属医院基础医学院,合肥市230601

出　　处：《实用肝脏病杂志》2015年第2期136-140,共5页Journal of Practical Hepatology

基　　金：安徽省教育厅自然科学基金资助项目(编号:KJ2014A107)

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）m RNA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 m RNA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 m RNA水平和XBP1 m RNA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HBs Ag〈1500IU/ml、1500-20000IU/ml和〉20000IU/ml组患者,GRP78 m RNA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1×10^3-10^5copies/ml组XBP1 m RNA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、HBe Ag阳性与阴性组间和胆红素正常与升高组间,以上三种基因m RNA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。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 ×10^3 to 105copies/ml was lower than in patients with higher serum HBV DNA load （〉1 ×10^5copies/ml）[（0.86 ±1.13） vs. （1.44±1.31）,P〈0.05];However,there existed no statis-tical differences as respect to the three mRNA levels among patients with different serum alanine amino-transferase,nor between patients with normal or ab-normal serum bilirubin,nor between HBeAg-positive and HBeAg-negative patients. Conclusion Endoplas-mic reticulum stress may be associated with the dis-ease progression in patients with chronic HBV infection.

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 

分 类 号：R512.62[医药卫生—内科学]