大鼠胰腺上皮内瘤变和胰腺癌模型血清蛋白质谱的差异表达

Differential expression of serum proteomic spectra in rat model of pancreatic intraepithelial neoplasia and dimethylbenzanthracene-induced pancreatic carcinoma

目的:利用表面增强激光解析离子化飞行时间质谱(SELDI-TOF MS)技术,分析由7,12-二甲基苯并蒽(DMBA)诱导建立的大鼠胰腺上皮内瘤变(PanIN)和胰腺癌(PC)模型血清蛋白质谱的差异表达.方法:40只♂清洁级SD大鼠为模型组,DMBA胰腺局部种植建立PanIN和PC模型,根据PanIN标准进行病理学分级.26只♂清洁级SD大鼠为正常对照组.采用SELDI-TOF MS和铜离子鳌合芯片(IMAC-Cu2+芯片)检测大鼠血清蛋白质谱,Biomarker Wizard3.0软件分析比较对照组、PanIN组和PC组之间的差异表达蛋白.结果:DMBA胰腺局部种植后共获得PC11例,PanIN18例.与对照组比较,PanIN组和PC组表达强度显著上调(P<0.001)的蛋白质峰有19个,显著下调(P<0.001)的蛋白质峰有11个;其中质荷比分别为5835.2、4087.3、4786.5、4800.5、3932.2、5765.9、5924.8、5001.9、3913.7的9个蛋白质峰表达强度在对照组、PanIN组和PC组呈逐级递增趋势,质荷比分别为1096.9、1478.9、8572.9、1007.1的4个蛋白质峰表达强度呈逐级递减趋势.结论:与正常大鼠比较,PanIN和PC模型大鼠血清蛋白质谱表达发生显著变化,这些差异表达蛋白质在胰腺癌中的作用值得进一步深入研究.

AIM： To investigate relationship between differential expression of serum proteomic spectra in rat model of pancreatic intraepithelial neoplasia （PanIN） and dimethylbenzanthracene -induced pancreatic carcinoma （PC） using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry （SELDI-TOFMS） technology. METHODS： Forty male SD rats were implanted with DMBA into the pancreas to induce rat model of PanIN and PC. Histopathology was evaluated according to PanIN classification system. And normal control group of twentysix male SD rats was established. The serum protein spectra were detected using IMAC-Cu^2＋ proteinchip and SELDI-TOF MS. The data were analyzed using Biomarker Wizard 3.0 Software of Ciphergen Biosystem Co. RESULTS： DMBA was implanted into pancreas of rats in PC group （n = 11） and PanIN group （n = 18）. Compared with the normal control group, there were significant differences （P 〈 0.001） of 30 protein peaks in PanIN and PC of which 19 protein peaks were up-regulated and 11 downregulated. The expression of 9 protein peaks, with a ratio of mass to charge （M/Z） of 5835.2, 4087.3, 4786.5, 4800.5, 3932.2, 5765.9, 5924.8, 5001.9, 3913.7 gradually increased from normal to PanIN and PC group, and 4 protein peaks with a M/Z ratio of 1096.9, 1478.9, 8572.9, 1007.1 gradually decreased. CONCLUSION： Serum proteomic spectra were differentially expressed in rat model of PanIN and PC. Identification and function of these differentially expressed proteins necessitate further investigation.