摘要
目的:探讨压力超负荷导致大鼠左心衰竭相关肺动脉高压(HF-PH)时血清代谢组及代谢通路的变化。方法:通过主动脉弓缩窄(TAC)建立大鼠压力超负荷左心衰竭模型,根据TAC术后不同时点分为0周组(n=6)、6周组(n=6)和9周组(n=6),另设假手术对照组(n=6)。行心脏彩超检测左室重构和心功能,通过心导管检测平均肺动脉压(mPAP),通过超高效液相色谱-四级杆飞行时间质谱(UPLC-QTOFMS)技术分析血浆代谢物,采用正交偏最小二乘判别分析(OPLS-DA)及t检验筛选HF-PH形成过程中差异性代谢物并进行代谢通路分析。结果:与0周组相比,心脏彩超提示TAC术后6周和9周组室间隔和左室后壁厚度增加,6周时左室射血分数(LVEF)的差异无统计学显著性,9周时LVEF减少[(67.09±2.61)%vs(82.91±7.79)%,n=6,P<0.01]。心导管检测发现,与0周组相比,术后6周mPAP增高,但仍在正常范围之内[(19.53±0.97)mmHg vs(15.81±0.78)mmHg,n=6,P<0.05],术后9周mPAP增高[(30.08±1.07)mmHg vs(15.81±0.78)mmHg,n=6,P<0.01],提示TAC术后6周肺动脉高压开始形成,9周发展为HF-PH。OPLS-DA分析提示6周和9周组代谢模式分离,根据VIP>1和P<0.05的筛选标准,两组间16个代谢物表达差异显著;进一步用KEGG分析提示初级胆汁酸合成途径变化显著;与该途径相关的代谢物有胆酸和鹅脱氧胆酸,ROC分析两者预测HF-PH的曲线下面积分别为0.929和0.905。结论:初级胆汁酸合成途径可能参与了HF-PH的形成和发展;胆酸和鹅脱氧胆酸可能成为HF-PH的预测标志物及治疗新靶点。
AIM:To investigate the changes of serum metabolome and metabolic pathways in the development of left heart failure-associated pulmonary hypertension(HF-PH)in rats of by untargeted ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-QTOFMS)methods.METHODS:Sprague-Dawley(SD)rats were used to construct left heart over-pressure heart failure model by transverse aortic constriction(TAC)surgery.The rats after TAC were further divided into 0-week,6-week and 9-week groups(n=6 each). Another 6 rats served as sham group. Echocardiography was performed to determine the cardiac remodeling and left heart function. Right cardiac catheterization was performed to measure the mean pulmonary artery pressure(mPAP). The plasma metabolites were detected by UPLC-QTOFMS and Q-TOFMS. The specific metabolites of the model were screened by orthogonal partial least squares discriminant analysis(OPLS-DA)and t-test. The metabolic pathways were analyzed by KEGG,and the predictive value of the screened metabolite was analyzed by receiver operating characteristic(ROC)curve.RESULTS:Compared with 0-week group,the thickness of interventricular septum and diastolic left ventricular posterior wall was increased in both 6-week group and 9-week group. No statistical significance in difference of left ventricular ejection fraction(LVEF)between 0-week group and 6-week group was observed. However,LVEF in 9-week group was decreased significantly compared with 0-week group[(67. 09±2. 61)% vs(82. 91±7. 79)%,n=6,P<0. 01]. The mPAP in 6-week group was increased but remained in the normal range compared with 0-week group[(19. 53±0. 97)mmHg vs(15. 81±0. 78)mmHg,n=6,P<0. 05]. However,mPAP in 9-week group was increased significantly compared with 0-week group[(30. 08±1. 07)vs(15. 81±0. 78)mmHg,n=6,P<0. 01]. The OPLS-DA analysis showed different metabolic patterns between 6-week group and 9-week group. Based on the criterion of variable importance in projection(VIP)>1 and P<0. 05,16 metabolites were screened. Further KEGG
作者
董博
谭兰兰
胡骏豪
牛欢
周骐
武晓静
DONG Bo;TAN Lan-lan;HU Jun-hao;NIU Huan;ZHOU Qi;WU Xiao-jing(Cardiovascular Department of Shenzhen University General Hospital,Shenzhen 518055,China;Cardiovascular Department of Chongqing Medical University Second Affiliated Hospital,Chongqing 400010,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2021年第10期1747-1754,共8页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.81270109
No.91539104)
广东省基础与应用基础研究基金项目(No.2019A1515011421)
深圳市自然科学基金基础研究面上项目(No.JCYJ20190808122207499)
深圳市重点实验室筹建项目(No.ZDSYS20190902093401689)。
关键词
心力衰竭
肺动脉高压
代谢组
初级胆汁酸
Heart failure
Pulmonary hypertension
Metabolome
Primary bile acid
