抗凋亡蛋白HAX-1过表达对心肌肥厚小鼠肝脏代谢组学的影响  

Effect of overexpression of anti-apoptotic protein HAX-1 on hepatic metabolomics in mice with hypertrophy

作　　者：王帅[1] 阴兆静 陈秀英[2] 徐霞[2] WANG Shuai;YIN Zhao-jing;CHEN Xiu-ying;XU Xia(Department of Pharmacy,Zhengzhou First People’s Hospital,Zhengzhou 450004;Department of Pharmacy,Zhengzhou University,Zhengzhou 450001)

机构地区：[1]郑州市第一人民医院药学部,郑州450004 [2]郑州大学药学院,郑州450001

出　　处：《中南药学》2020年第1期25-31,共7页Central South Pharmacy

基　　金：国家自然科学基金(编号：81270270)

摘　　要：目的考察抗凋亡蛋白HAX-1的表达对小鼠心肌肥厚模型的影响。方法构建重组腺病毒载体Ad-HAX-1,使HAX-1过表达,以含绿色荧光蛋白的腺病毒载体(Ad-GFP)作为对照组。小鼠随机分为假手术组(Sham组)、主动脉弓缩窄(TAC组)手术组及HAX-1过表达组(HAXOP组)。TAC组在手术前3 d心肌内注射Ad-GFP,HAXOP组在手术前3 d心肌内注射Ad-HAX-1,6周后动物安乐死,取心脏和肝脏,采用Western blot检测小鼠心肌组织中HAX-1的表达;采用超高效液相色谱-四极杆静电场轨道阱高分辨质谱串联技术结合主成分分析(PCA)、偏最小二乘判别分析(PLS-DA)和正交偏最小二乘判别分析(OPLS-DA)对不同组小鼠的肝脏进行代谢组学的研究,筛选出差异化合物并进一步研究其代谢通路。结果HAX-1蛋白过表达改变甘油磷脂代谢、糖酵解等代谢通路。结论HAX-1过表达可改善心肌肥厚,其作用机制主要与甘油磷脂代谢有关。Objective To determine the effect of anti-apoptotic protein hematopoietic-substrate-1 associated protein X-1(HAX-1)on cardiac hypertrophy model.Methods The recombinant adenoviral vector Ad-HAX-1 was constructed to over-express HAX-1 and a green fluorescent protein-containing adenovirus vector(Ad-GFP)was used as a control group.The mice were randomly divided into a Sham group(Sham group),a transverse aortic constriction(TAC)group and a HAX-1 overexpression group.The TAC group and HAXOP group respectively were intramyocardially injected Ad-GFP and Ad-HAX-1 three days before the surgery,while the mice were only opened cardiac in the Sham group.All mice were euthanized after 6 weeks and the hearts and livers were taken.UHPLC-Q-Exactive MS combined with principal component analysis,partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis was used.A metabonomics study was performed on the livers of different groups of mice to screened out the different compounds and further determine their metabolic pathways.Results The HAX-1 gene mainly altered the glycerophospholipid metabolism.Conclusion Overexpression of HAX-1 helps improve cardiac hypertrophy,and its mechanism is related to energy metabolism.

关 键 词：代谢组学 抗凋亡蛋白HAX-1 心肌肥厚 

分 类 号：R285[医药卫生—中药学]