人风湿性心脏病心肌的蛋白质组研究
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摘要
目的：通过对风湿性心脏病患者及二尖瓣脱垂患者的左心室乳头肌的蛋白质组分析与比较,建立人风湿性心脏病心肌二维凝胶电泳图谱,寻找并鉴定可以代表风湿性心脏炎心肌损伤的蛋白质,并探讨其在风湿性心脏病心肌损伤病理生理过程中的意义与机制。
方法：选取风湿性心脏病二尖瓣病变患者为研究组,二尖瓣脱垂患者为对照组。采取术中切得的二尖瓣腱索根部分离左室乳头肌同时采集临床资料。将两组患者配对后行二维凝胶内差示电泳,两组间比较的差异蛋白点用T-test p Value和Average Ratio来筛选,将筛选所得的差异点蛋白行基质辅助激光解析电离飞行时间质谱分析,检索数据库鉴定蛋白质。
结果：共有9组一一配对左室乳头肌样本行二维凝胶内差示电泳,行Decyder6.5软件分析后得到风湿性心脏病左室乳头肌蛋白质二维凝胶电泳谱,与对照组比较后有39个位点有统计学差异,其中28个位点切胶成功并行质谱分析,鉴定出12种已知的蛋白质,其中3个蛋白丰度有显著差异：热休克蛋白60,AV-RATIO为-3.17；结蛋白,AV-RATIO为-1.62；蛋白酶体,AV-RATIO为-1.71,并且有100%阳性率。
结论：通过本次研究,我们建立了人风湿性心脏病心肌的二维凝胶内电泳图谱,并且发现热休克蛋白60、结蛋白及蛋白酶体的显著增高,提示其可能与风湿性心脏病的特征性心肌炎症有关,特别是热休克蛋白60可能在风湿性心脏病心肌的自身免疫性炎症进程具有关键作用。
Objective:By means of proteomic analysis and comparison of the left ventricular papillary muscles from patients with rheumatic heart disease or mitral valve prolapse, we tried to establish the human myocardial two-dimensional gel electrophoresis (2-DE) map in rheumatic heart disease, looking for and identified the characteristic proteins on behalf of the chronic inflammatory myocardium injury after rheumatic fever, and to explore their significance and mechanism in the pathophysiological process of the myocardial lesion in rheumatic heart disease.
Methods:We defined the patients with rheumatic mitral valve disease as experimental group, patients with mitral valve prolapse as the control group. Took the left ventricular papillary muscle from resected mitral valve during the mitral valve replacemen, at the same time to collect the clinical material. Matched the two groups of patients, underwent two-dimensional differential in-gel electrophoresis (DIGE). We used T-test, P-Value and Average Ratio to screen the differentially expressed protein sites between the two groups.Then the sites indicated statistical difference (P<0.05) were identified by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) and database searching.
Results:A total of9pairs of the left ventricular papillary muscles underwent DIGE. We established the human myocardial2-DE map in rheumatic heart disease by the analysis of Decyder6.5. Compared with the control group,39protein sites indicated statistical differences, of which28gel sites were successfully cut for MALDI-TOF-MS.12known proteins were identified, in which there were3protein abundance indicated significantly difference:heat shock protein60(HSP60), the AV-RATIO was-3.17; desmin, the AV-RATIO was-1.62; proteasome, the AV-RATIO was-1.71, and their probability of appearance was100%.
Conclusion:In this study, we established the human myocardial2-DE map in rheumatic heart disease, and found that HSP60, desmin and proteasome were significantly higher expressed, suggesting they could be relative to characteristic myocarditis in rheumatic heart disease. It must be noted that HSP60may play a key role in the autoimmune inflammatory process in rheumatic heart disease.
方法：选取风湿性心脏病二尖瓣病变患者为研究组,二尖瓣脱垂患者为对照组。采取术中切得的二尖瓣腱索根部分离左室乳头肌同时采集临床资料。将两组患者配对后行二维凝胶内差示电泳,两组间比较的差异蛋白点用T-test p Value和Average Ratio来筛选,将筛选所得的差异点蛋白行基质辅助激光解析电离飞行时间质谱分析,检索数据库鉴定蛋白质。
结果：共有9组一一配对左室乳头肌样本行二维凝胶内差示电泳,行Decyder6.5软件分析后得到风湿性心脏病左室乳头肌蛋白质二维凝胶电泳谱,与对照组比较后有39个位点有统计学差异,其中28个位点切胶成功并行质谱分析,鉴定出12种已知的蛋白质,其中3个蛋白丰度有显著差异：热休克蛋白60,AV-RATIO为-3.17；结蛋白,AV-RATIO为-1.62；蛋白酶体,AV-RATIO为-1.71,并且有100%阳性率。
结论：通过本次研究,我们建立了人风湿性心脏病心肌的二维凝胶内电泳图谱,并且发现热休克蛋白60、结蛋白及蛋白酶体的显著增高,提示其可能与风湿性心脏病的特征性心肌炎症有关,特别是热休克蛋白60可能在风湿性心脏病心肌的自身免疫性炎症进程具有关键作用。
Objective:By means of proteomic analysis and comparison of the left ventricular papillary muscles from patients with rheumatic heart disease or mitral valve prolapse, we tried to establish the human myocardial two-dimensional gel electrophoresis (2-DE) map in rheumatic heart disease, looking for and identified the characteristic proteins on behalf of the chronic inflammatory myocardium injury after rheumatic fever, and to explore their significance and mechanism in the pathophysiological process of the myocardial lesion in rheumatic heart disease.
Methods:We defined the patients with rheumatic mitral valve disease as experimental group, patients with mitral valve prolapse as the control group. Took the left ventricular papillary muscle from resected mitral valve during the mitral valve replacemen, at the same time to collect the clinical material. Matched the two groups of patients, underwent two-dimensional differential in-gel electrophoresis (DIGE). We used T-test, P-Value and Average Ratio to screen the differentially expressed protein sites between the two groups.Then the sites indicated statistical difference (P<0.05) were identified by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) and database searching.
Results:A total of9pairs of the left ventricular papillary muscles underwent DIGE. We established the human myocardial2-DE map in rheumatic heart disease by the analysis of Decyder6.5. Compared with the control group,39protein sites indicated statistical differences, of which28gel sites were successfully cut for MALDI-TOF-MS.12known proteins were identified, in which there were3protein abundance indicated significantly difference:heat shock protein60(HSP60), the AV-RATIO was-3.17; desmin, the AV-RATIO was-1.62; proteasome, the AV-RATIO was-1.71, and their probability of appearance was100%.
Conclusion:In this study, we established the human myocardial2-DE map in rheumatic heart disease, and found that HSP60, desmin and proteasome were significantly higher expressed, suggesting they could be relative to characteristic myocarditis in rheumatic heart disease. It must be noted that HSP60may play a key role in the autoimmune inflammatory process in rheumatic heart disease.
引文
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