文献类型：期刊文献

英文题名：Huoxue Huatan Decoction Ameliorates Myocardial Ischemia/Reperfusion Injury in Hyperlipidemic Rats via PGC-1α-PPARα and PGC-1α-NRF1-mtTFA Pathways

作者：Lin, Fei[1];Tan, Yu-Qing[2,3];He, Xuan-Hui[2];Guo, Li-Li[2];Wei, Ben-Jun[4];Li, Jun-Ping[2];Chen, Zhong[2];Chen, Heng-Wen[2];Wang, Jie[2]

第一作者：Lin, Fei

通信作者：Chen, HW[1];Wang, J[1]

机构：[1]Xinxiang Med Univ, Affiliated Hosp 1, Ctr Heart, Xinxiang, Henan, Peoples R China;[2]China Acad Chinese Med Sci, Dept Cardiol, Guanganmen Hosp, Beijing, Peoples R China;[3]Beijing Univ Chinese Med, Grad Sch, Beijing, Peoples R China;[4]Gansu Univ Chinese Med, Key Lab Minist Educ Dept Lanzhou Prov & Dunhuang, Lanzhou, Peoples R China

第一机构：Xinxiang Med Univ, Affiliated Hosp 1, Ctr Heart, Xinxiang, Henan, Peoples R China

通信机构：[1]corresponding author), China Acad Chinese Med Sci, Dept Cardiol, Guanganmen Hosp, Beijing, Peoples R China.

年份：2020

卷号：11

外文期刊名：FRONTIERS IN PHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000576201100001)】；

基金：This study was supported by the National Major Scientific and Technological Special Project for "Significant New Drugs Development" (No. 2012ZX09102201), the National Natural Science Foundation of China (No. 81973836), the China Association for Science and Technology Youth Talent Project (No. 2017QNRC001), and the China Academy of Chinese Medical Sciences-Traditional Chinese Medicine Science and Technology Achievement Leading Project (No. ZZ13-ZD-04).

语种：英文

外文关键词：Huoxue Huatan Decoction; hyperlipidemia; ischemia/reperfusion (I/R); mitochondria; PGC-1 alpha

摘要：Objective: The aim of this study was to eluc\idate the preventive and therapeutic effects and the underlying mechanisms of Huoxue Huatan Decoction (HXHT) on myocardial ischemia/reperfusion (I/R) injury in hyperlipidemic rats. Methods: An I/R model was established in hyperlipidemic Wistar rats. After 4-8 weeks of HXHT treatment, the physical signs of rats were observed. Lipid metabolism, myocardial enzyme spectrum, cardiac function, myocardial histomorphology, and mitochondrial biosynthesis were investigated by a biochemical method, ultrasonography, electron microscopy, pathological examination, real-time PCR, and Western blot. Results: HXHT can affect lipid metabolism at different time points and significantly reduce the levels of cholesterol (CHO), triglyceride (TG), high-density lipid-cholesterol (HDL-C), and low-density lipid-cholesterol (LDL-C) in hyperlipidemic rats (P< 0.05 orP< 0.01); it can significantly reduce the levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), reduce the myocardial infarct size and myocardial ischemic area, and improve cardiac function. The results of myocardial histomorphology showed that HXHT could protect myocardial cells, relieve swelling, reduce the number of cardiac lipid droplets, and improve myocardial mitochondrial function. HXHT could significantly increase the levels of total superoxide dismutase (T-SOD) and succinate dehydrogenase (SDH) (P< 0.05 orP< 0.01), increase CuZn-superoxide dismutase (CuZn-SOD) and glutathione-peroxidase (GSH-Px) levels, and decrease the levels of malondialdehyde (MDA) (P< 0.05); it could increase the mRNA and protein expression levels of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha), peroxisome proliferator-activated receptor alpha (PPAR alpha), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (mtTFA) (P< 0.05 orP< 0.01), and increase the synthesis of mitochondrial DNA (mtDNA) (P< 0.01). Conclusion: HXHT can reduce myocardial I/R injury in hyperlipidemic rats. The protective mechanisms may involve a reduction in blood lipids, enhancement of PGC-1 alpha-PPAR alpha pathway activity, and, subsequently, an increase in fatty acid beta-oxidation, which may provide the required input for mitochondrial energy metabolism. HXHT can additionally enhance PGC-1 alpha-NRF1-mtTFA pathway activity and, subsequently, increase the antioxidant capacity, promote mtDNA synthesis, and reduce mitochondrial damage. The two pathways use PGC-1 alpha as the intersection point to protect mitochondrial structure and function, reduce I/R-induced injury, and improve cardiac function.