基于脂质代谢组学研究芪参益气滴丸保护高脂血症心肌缺血再灌注损伤大鼠心肌损伤的机制

Study on the mechanism of protecting the myocardial injury in rats with hyperlipidemia myocardial ischemia-reperfusion injury based on lipid metabolomics

[目的]基于脂质组学方法考察芪参益气滴丸(QSYQ)对高脂血症心肌缺血再灌注损伤大鼠脂质代谢的影响,以探讨其保护心肌缺血再灌注损伤的作用机制。[方法]采用高脂饮食喂养复制高脂血症大鼠模型,采用结扎左前降支方法建立大鼠心肌缺血再灌注损伤模型,实验分组为假手术组、模型组、芪参益气滴丸低、中、高剂量组(62.5、135、270 mg/kg),于再灌注3 h后取血检测肌酸激酶(CK)、乳酸脱氢酶(LDH)以及血脂水平;取心肌组织TTC染色考察梗死面积。采用UPLC-Orbitrap质谱系统的非靶向脂质组学分析平台进行心肌组织匀浆液的脂质组学研究。[结果]与假手术组比较,模型组大鼠血清低密度脂蛋白(LDL)、总胆固醇(TC)、CK和LDH明显增加(P<0.05),心肌梗死现象较为严重;与模型组相比,QSYQM组大鼠血清CK含量和心肌梗死面积显著降低(P<0.05),并且LDL和TC显著降低。脂质组学共鉴定心脏脂质亚类32种,脂质分子1141种,差异脂质分子筛选结果显示:模型组和假手术组有显著差异脂质分子44种,芪参益气滴丸中剂量组和模型组有差异脂质分子13种,其中芪参益气滴丸治疗后与模型组出现显著相反趋势的脂质分子有6种(P<0.05,VIP>1.0),分别为胺神经酰胺(Cer,d18∶1/18∶0)+H、磷脂酰乙醇胺(PE,16∶0p/22∶4)+H、PE(18∶2p/18∶2)+H、溶血磷脂酰胆碱(LPC,18∶0)+H、LPC(18∶0)+Na以及磷脂酰胆碱(PC,16∶0/18∶1)+HCOO。[结论]本研究利用心肌组织脂质组学技术发现了芪参益气滴丸通过改善心脏脂质代谢发挥保护高脂血症心肌缺血再灌注心肌损伤的线索,进一步丰富了芪参益气滴丸心肌保护的现代研究。

[Objective]To investigated the effect of Qishen Yiqi Dropping Pills(QSYQ)on lipid metabolism in rats with hyperlipidemia myocardial ischemia-reperfusion injury based on the lipidomics method,to explore the protecting mechanism against myocardial ischemia-reperfusion injury.[Methods]Rat model of hyperlipidemia was induced by using high-fat diet,and the left anterior descending branch was ligated to induce the model of myocardial ischemia and reperfusion injury.Sham operation group,model group,QSYQ low,medium and high dose group(62.5,135,270 mg/kg)were set in the present study.Creatine kinase(CK),lactic acid dehydrogenase(LDH)and lipid level were checked 3 hours after I/R.TTC staining was used to examine the myocardial infarction(MI)area.The lipidomics study of myocardial tissue homogenates was performed by using the UPLC-Orbitrap mass spectrometry system.[Results]Compared with the sham group,the serum LDL,TC,CK and LDH in the model group were significantly increased(P<0.05),and the myocardial infarction was more serious;Compared with the model group,the serum CK content and MI area were significantly decreased in the QSYQM rats(P<0.05),and the LDL and TC were decreased significantly.The 32 cardiac lipid subclasses and 1141 lipid molecules were identified by lipidomics.The results of different lipid molecules showed that there were 44 significantly different lipid molecules between the model group and the sham group.There were 13 different lipid molecules in the QSYQM and the model group,and 6 lipid molecules[Cer(d18∶1/18∶0)+H,PE(16∶0p/22∶4)+H,PE(18∶2p/18∶2)+H,LPC(18∶0)+H,LPC(18∶0)+Na,and PC(16∶0/18∶1)+HCOO]with a significant opposite trend with the model group after the treatment(P<0.05,VIP>1.0).[Conclusion]We found that QSYQ protects from myocardial ischemia and reperfusion injury in hyperlipidemia by improving cardiac lipid metabolism,and this research would further enriched the modern research on myocardial protection by QSYQ.