高血压病痰湿壅盛证患者血清蛋白质组学研究

目的：对高血压病痰湿壅盛证患者血清蛋白质组学进行研究,试图寻找与痰湿壅盛证相关的特异蛋白质。方法：纳入59例高血压患者,将其分为痰湿壅盛组（39例）和非痰湿壅盛组（20例）,并选择30例健康体检者作为正常对照。采用弱阳离子纳米磁性微球捕获血清中的蛋白质,Ciphergen PBS-Ⅱc型蛋白质芯片阅读检测仪绘制成蛋白指纹图谱。所有蛋白指纹图谱采用Biomarker Wizard3.1分析之后用Biomarker PatternsSoftware5.0识别痰湿壅盛证特异表达的蛋白质,并建立诊断模型。结果：高血压病痰湿壅盛证（痰湿壅盛）与对照组之间共检测出有显著差异的蛋白质峰102个（P〈0.05）。以质荷比（mass to charge ratio,m/z）为9334.958（表达增高）、9280.191（表达降低）、8030.794（表达增高）和2941.551（表达增高）4个蛋白峰组成的诊断模型能很好地将痰湿壅盛区分出来。该诊断模型的敏感性为93.103%（27/29）,特异性为92%（23/25）,假阳性率为8%（2/25）,假阴性率为6.897%（2/29）,Youden指数为85.103%。盲法检验其敏感性为90%（9/10）,特异性为88%（22/25）,假阳性率为12%（3/25）,假阴性率为10%（1/10）,Youden指数为78%。结论：差异表达的蛋白质很可能是高血压病痰湿壅盛证的物质基础,筛选出的差异蛋白质是该证型患者血清蛋白标记物中区别于正常人和非此证型的高血压患者的共性特异蛋白。以此建立的分子生物学诊断模型,为中医辨证提供了一种更加客观准确的辨证手段。

Serum proteomes of hypertension patients with abundant phlegm-dampness

Objective: To study the serum proteomes of essential hypertension (EH) patients with abundant phlegm-dampness, and try to find special proteins associated with abundant phlegm-dampness syndrome.Methods: Fifty-nine hypertension patients were included, and the patients were divided into abundant phlegm-dampness syndrome group (39 cases) and non-phlegm-dampness syndrome group (20 cases). To find the special proteins associated with abundant phlegm-dampness, the EH patients with non-phlegm-dampness and another 30 healthy persons were regarded as control. Weak cation nano-magnetic beads were used to capture proteins in serum, and proteomic fingerprint was made by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). All the proteomic fingerprints were analyzed by Biomarker Wizard 3.1 Software. Then Biomarker Patterns Software (BPS) 5.0 was used to identify the differentiated proteins, which could induce phlegm-dampness.Results: There were 102 differentiated protein peaks between abundant phlegm-dampness and the control group. The best markers of abundant phlegm-dampness were protein peaks with the mass to charge ratio (m/z) of 9 334. 958 m/z (the expression increased), 9 280. 191 m/z (the expression decreased), 8 030.794 m/z (the expression increased), and 2 941.551 m/z (the expression increased). These four protein peaks found by BPS could induce abundant phlegm-dampness. They could be used to separate the abundant phlegm-dampness syndrome from the healthy persons and the hypertension patients with non-phlegm-dampness. The sensitivity of the model was 93.103% (27/29), specificity was 92% (23/25), false positive rate was 8% (2/25), false negative rate was 6.897% (2/29) and Youden's index was 85.103%. Blind test data indicated a sensitivity of 90% (9/10) and a specificity of 88% (22/25), and the false positive rate was 12% (3/25), false negative rate was 10% (1/10), and Youden's index was 78%.Conclusion: The differentiated proteins between the abundant phlegm-dampness group and the control group are the material foundation of abundant phlegm-dampness. The selected differentiated proteins can be used to distinguish the EH patients with abundant phlegm-dampness from the healthy persons and the EH patients with non-phlegm-dampness. The molecular biology diagnosis model can offer an objective and accurate way for TCM syndrome differentiation.