替米沙坦对自发性高血压大鼠左心室肥厚相关蛋白质谱的影响  

Effects of telmisartan on left ventricular hypertrophy related protein profiles in spontaneously hypertensive rats

作　　者：冯宇 周曼丽 王健章 张家齐 钱舒乐 简维雄[1] FENG Yu;ZHOU Man-li;WANG Jian-zhang;ZHANG Jia-qi;QIAN Shu-le;JIAN Wei-xiong(Hunan University of Traditional Chinese Medicine,Changsha Hunan 410208,China)

机构地区：[1]湖南中医药大学,湖南长沙410208

出　　处：《中华高血压杂志》2020年第8期750-756,共7页Chinese Journal of Hypertension

基　　金：国家自然科学基金项目(81774207,81973753);湖南省自然科学基金项目(2018JJ2291)。

摘　　要：目的研究替米沙坦对自发性高血压大鼠(SHR)左心室心肌组织蛋白质谱的影响。方法将16只SHR随机分为对照组、替米沙坦组,分别给予无菌注射用水(10 mL/kg)和替米沙坦(4.33 mg/kg)进行灌胃,另外选取8只Wistar-Kyoto(WKY)大鼠给予无菌注射用水(10 mL/kg)进行灌胃(WKY组),连续给药12周。12周后处死大鼠,取心脏样本制成蛋白质剂。随后将蛋白质剂分离部分进行同位素标记相对和绝对定量(iTRAQ)、强阳离子交换柱液相分离并用串联质谱仪进行质谱鉴定。最后通过差异蛋白通路富集分析选出与通路相关的蛋白质及其参与的生化代谢途径和信号转导途径。结果与通路相关的总共23个差异蛋白,与替米沙坦组比较,SHR组上调的差异蛋白:促蛋白激酶激酶3、转胶蛋白、结合珠蛋白亚型2;下调的差异蛋白:血管性血友病因子(片段)、激肽原1、小核糖核蛋白相关蛋白、纤维蛋白原β链、蛋白质质量3(片段)、蛋白酶体、热休克蛋白27相关蛋白1、腱糖蛋白X、纤维粘连蛋白亚型2、转铁蛋白受体蛋白、血小板1、组织蛋白酶L1、补体因子B,同种型CRAb、纤维蛋白原异构体、免疫球蛋白重链(γ多肽)、α1抗蛋白酶。结论替米沙坦可能通过热休克蛋白27、纤维蛋白原、纤维粘连蛋白、蛋白酶体26s、转胶蛋白这些差异蛋白及其参与的生化代谢途径、信号转导途径影响高血压大鼠左心室肥厚。Objective To investigate the effects of telmisartan on the protein profiles of left ventricular myocardial tissue in spontaneously hypertensive rats(SHR).Methods Sixteen SHR were randomly divided into the control group and the telmisartan group.They were treated with sterile water for injection(10 mL/kg)or telmisartan(4.33 mg/kg)by intragastric administration.Wistar-Kyoto(WKY)rats treated with sterile water for injection(10 mL/kg)served as control.The treatment period was 12 weeks.After 12 weeks,those rats were sacrificed,and their heart samples were collected to make protein preparations.Subsequently,the separated part of the protein agent was subjected to isotope-labeled relative and absolute quantitative(iTRAQ)labeling and strong cation exchange column liquid phase separation and mass spectrometry identification using a tandem mass spectrometer.Finally,pathway-related proteins and their biochemical metabolic pathways and signal transduction pathways were selected via the differential protein pathway enrichment analysis.Results There were 23 differential proteins related to the pathway in total.Compared with the telmisartan group,the up-regulated differential proteins in the SHR group were prokinin kinase 3,transgelin,and haptoglobin subtype 2.The down-regulated differential proteins in the SHR group were as follows:von Willebrand factor(fragment),kininogen 1,small ribonucleoprotein-related protein,fibrinogen beta chain,protein mass 3(fragment),proteasome,heat shock protein 27-related protein 1,tenascin X,fibronectin subtype 2,transferrin receptor protein,platelets 1,cathepsin L1,complement factor B,isoform CRAb,fibrinogen isomer,immunoglobulin heavy chain(γpolypeptide)andα1 anti-protease.Conclusion Telmisartan may affect the left ventricular hypertrophy in hypertensive rats through heat shock protein 27,fibrinogen,fibronectin,proteasome 26 s and transgelin,as well as their biochemical metabolic pathways and signal transduction pathways.

关 键 词：替米沙坦 左心室肥厚 高血压 大鼠 蛋白质组学 

分 类 号：R965[医药卫生—药理学]