Trak-Smayra V, Dargere D, Noun R, Albuquerque M, Yaghi C, Gannagé-Yared M-H, Bedossa P, Paradis V
Centre de recherche Biomédical Bichat Beaujon, INSERM U773, Paris, France.
Gut. 2009 Jun;58(6):825-32. doi: 10.1136/gut.2007.140087. Epub 2008 Apr 10.
Chronic liver diseases, including cirrhosis, may develop in obese patients. Steatosis and non-alcoholic steatohepatitis (NASH) are risk factors for progression to fibrosis. To date, diagnosis of steatosis and NASH relies on liver biopsy. The aim of the study was to identify serum markers of steatosis and NASH in obese patients using SELDI-TOF ProteinChip.
Eighty obese non-alcoholic patient candidates for bariatric surgery and devoid of hepatitis B and C infection were selected. Serum samples were collected before surgery and at 6 months after surgery for 33 of these patients. Wedge liver biopsy was performed at the time of bariatric surgery. Twenty-four serum samples from healthy blood donors served as controls. The protein profiles of each serum were assessed using SELDI-TOF ProteinChip technology and were compared according to liver histological lesions.
Twenty-four obese patients (30%) had non-significant liver lesions, 32 (40%) had significant steatosis and 24 (30%) had NASH. Comparison of serum protein profiles according to liver lesions identified three peaks (CM10-7558.4, CM10-7924.2 and Q10-7926.9) the intensity of which significantly increased according to the severity of the liver lesions (steatosis and NASH) and returned to normal after bariatric surgery. None was correlated with either liver function tests or metabolic parameters. Identification using immunoSELDI assay characterised these peaks as the double charged ions of alpha- and beta-haemoglobin subunits.
The differential proteomic method demonstrated changes in serum protein profiles in obese patients according to severity of liver lesions. Free haemoglobin subunits may serve as a serum biomarker of the severity of liver damages.
肥胖患者可能会发展为慢性肝病,包括肝硬化。脂肪变性和非酒精性脂肪性肝炎(NASH)是纤维化进展的危险因素。迄今为止,脂肪变性和NASH的诊断依赖于肝活检。本研究的目的是使用表面增强激光解吸电离飞行时间质谱(SELDI-TOF)蛋白质芯片鉴定肥胖患者中脂肪变性和NASH的血清标志物。
选择80例拟行减肥手术的肥胖非酒精性患者,这些患者无乙肝和丙肝感染。其中33例患者在手术前和术后6个月采集血清样本。在减肥手术时进行楔形肝活检。24份来自健康献血者的血清样本作为对照。使用SELDI-TOF蛋白质芯片技术评估每份血清的蛋白质谱,并根据肝脏组织学病变进行比较。
24例肥胖患者(30%)有非显著性肝脏病变,32例(40%)有显著性脂肪变性,24例(30%)有NASH。根据肝脏病变比较血清蛋白质谱,确定了三个峰(CM10-7558.4、CM10-7924.2和Q10-7926.9),其强度根据肝脏病变(脂肪变性和NASH)的严重程度显著增加,减肥手术后恢复正常。这些峰均与肝功能检查或代谢参数无关。使用免疫SELDI分析鉴定这些峰为α和β血红蛋白亚基的双电荷离子。
差异蛋白质组学方法显示肥胖患者血清蛋白质谱根据肝脏病变严重程度而变化。游离血红蛋白亚基可能作为肝脏损伤严重程度的血清生物标志物。