平肝潜阳方治疗前后高血压病肝阳上亢证大鼠肾上腺组织蛋白表达变化的蛋白质组学研究  

Adrenal protein expressions after Pinggan Qianyang Formula treatment in hypertensive rats with liver-yang hyperactivity:a comparative proteomic analysis

作　　者：张莺[1] 陈泽奇[1] 钟广伟[1] 

机构地区：[1]中南大学湘雅医院中西医结合研究所,湖南长沙410008

出　　处：《中西医结合学报》2008年第7期729-737,共9页Journal of Chinese Integrative Medicine

基　　金：国家自然科学基金面上资助课题(青年基金)(No30500644;No30407211)

摘　　要：目的:从蛋白质组学水平探讨大鼠高血压肝阳上亢证发生机制及平肝潜阳方治疗肝阳上亢证的分子机制,为治疗高血压肝阳上亢证寻找新的药物标志蛋白提供理论和实验依据。方法:以自发性高血压大鼠(spontaneous hypertensive rat,SHR)加灌服附子汤法制备高血压肝阳上亢证大鼠模型,二维凝胶电泳分离大鼠肾上腺蛋白质,获得差异表达蛋白质;利用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)和数据库分析鉴定差异表达蛋白质。结果:高血压肝阳上亢证大鼠模型复制成功,平肝潜阳法治疗后易激惹程度和结膜充血减轻,收缩压下降(P<0.05,P<0.01)。通过点检测后,发现12个具有明显表达差异的蛋白质斑点,经鉴定可以确认的蛋白质点有8个,其中2个蛋白点为同一蛋白。其中异柠檬酸脱氢酶、类固醇合成急性调节蛋白在模型组表达较正常组上调,在治疗组重新下调至前水平;铁轻链蛋白、Tu翻译延长因子、鸟苷酸解离抑制因子、黄素还原酶、Basic转录因子3在模型组表达较正常组下调,在治疗组重新上调至前水平。结论:成功鉴定了高血压肝阳上亢证大鼠平肝潜阳方治疗前后肾上腺组织差异表达蛋白,为深入研究高血压病肝阳上亢证的病理机制及平肝潜阳方治疗的分子机制奠定了基础。Objective： To explore the pathogenic mechanism of liver-yang hyperactivity type of hypertension and to observe the effects of Pinggan Qianyang Formula （PGQYF）, a compound of traditional Chinese herbals for calming the liver and suppressing yang, so as to provide experimental evidence for new marker proteins of drug therapy. Methods： A rat model of liver-yang hyperactivity was prepared with spontaneous hypertensive rats （SHRs） by administration of Aconiti Praeparatae Decoction. Adrenal proteins were separated by 2D gel electrophoresis （2-DE）. The differentially expressed proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry （MALDI-TOF-MS） and database analysis. Results. The rat model of liver-yang hyperactivity was successfu decrease the grades of irritability, conjunctival congestion and systo ly reproduced, and the PGQYF could c blood pressure of the rats （ P〈0.05, P〈0. 01）. After analysis, twelve obviously differentially expressed proteins were found, eight of which were identified. The expression levels of isocitrate dehydrogenase and steroidogenic acute regulatory protein in the untreated group were up-regulated as compared with those in the normal control group, and down-regulated in the treatment group. The expression levels of ferritin light chain, elongation factor Tu, Rho GDP disassociation inhibitor 1, flavin reductase and basic transcription factor 3 in the untreated group were downregulated as compared with those in the normal control group, and up-regulated in the treatment group. Conclusion： Differentially expressed adrenal proteins in SHRs with live-yang hyperactivity are successfully identified. This approach may lay a foundation for the further investigation of pathogenic mechanisms in hypertension with liver-yang hyperactivity and the mechanisms of PGQYF treatment.

关 键 词：高血压 肝阳上亢证 平肝潜阳方 蛋白质组学 肾上腺 大鼠 

分 类 号：R259[医药卫生—中西医结合]