Huoxue Huatan Decoction Ameliorates Myocardial Ischemia/Reperfusion Injury in Hyperlipidemic Rats via PGC-1α–PPARα and PGC-1α–NRF1–mtTFA Pathways
ObjectiveThe 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.MethodsAn I/R model was established in hyperlipidemic Wistar rats. After 4–8...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-09-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.546825/full |
| _version_ | 1819058133516943360 |
|---|---|
| author | Fei Lin Yu-Qing Tan Yu-Qing Tan Xuan-Hui He Li-Li Guo Ben-Jun Wei Jun-Ping Li Zhong Chen Heng-Wen Chen Jie Wang |
| author_facet | Fei Lin Yu-Qing Tan Yu-Qing Tan Xuan-Hui He Li-Li Guo Ben-Jun Wei Jun-Ping Li Zhong Chen Heng-Wen Chen Jie Wang |
| author_sort | Fei Lin |
| collection | DOAJ |
| description | ObjectiveThe 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.MethodsAn 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.ResultsHXHT 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 or P < 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 or P < 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-1α), peroxisome proliferator-activated receptor alpha (PPARα), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (mtTFA) (P < 0.05 or P < 0.01), and increase the synthesis of mitochondrial DNA (mtDNA) (P < 0.01).ConclusionHXHT can reduce myocardial I/R injury in hyperlipidemic rats. The protective mechanisms may involve a reduction in blood lipids, enhancement of PGC-1α–PPARα pathway activity, and, subsequently, an increase in fatty acid β-oxidation, which may provide the required input for mitochondrial energy metabolism. HXHT can additionally enhance PGC-1α–NRF1–mtTFA pathway activity and, subsequently, increase the antioxidant capacity, promote mtDNA synthesis, and reduce mitochondrial damage. The two pathways use PGC-1α as the intersection point to protect mitochondrial structure and function, reduce I/R-induced injury, and improve cardiac function. |
| first_indexed | 2024-12-21T13:50:21Z |
| format | Article |
| id | doaj.art-3038a45a81f34ee79abab4f20352b67a |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-21T13:50:21Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-3038a45a81f34ee79abab4f20352b67a2022-12-21T19:01:42ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-09-011110.3389/fphar.2020.546825546825Huoxue Huatan Decoction Ameliorates Myocardial Ischemia/Reperfusion Injury in Hyperlipidemic Rats via PGC-1α–PPARα and PGC-1α–NRF1–mtTFA PathwaysFei Lin0Yu-Qing Tan1Yu-Qing Tan2Xuan-Hui He3Li-Li Guo4Ben-Jun Wei5Jun-Ping Li6Zhong Chen7Heng-Wen Chen8Jie Wang9Heart Center of Xinxiang Medical University, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, ChinaDepartment of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaGraduate School, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaDepartment of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaKey Laboratory of Ministry of Education Department of Lanzhou Province and Dunhuang Medical Transformation, Gansu University of Chinese Medicine, Lanzhou, ChinaDepartment of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaDepartment of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaDepartment of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaDepartment of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaObjectiveThe 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.MethodsAn 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.ResultsHXHT 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 or P < 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 or P < 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-1α), peroxisome proliferator-activated receptor alpha (PPARα), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (mtTFA) (P < 0.05 or P < 0.01), and increase the synthesis of mitochondrial DNA (mtDNA) (P < 0.01).ConclusionHXHT can reduce myocardial I/R injury in hyperlipidemic rats. The protective mechanisms may involve a reduction in blood lipids, enhancement of PGC-1α–PPARα pathway activity, and, subsequently, an increase in fatty acid β-oxidation, which may provide the required input for mitochondrial energy metabolism. HXHT can additionally enhance PGC-1α–NRF1–mtTFA pathway activity and, subsequently, increase the antioxidant capacity, promote mtDNA synthesis, and reduce mitochondrial damage. The two pathways use PGC-1α as the intersection point to protect mitochondrial structure and function, reduce I/R-induced injury, and improve cardiac function.https://www.frontiersin.org/article/10.3389/fphar.2020.546825/fullHuoxue Huatan Decoctionhyperlipidemiaischemia/reperfusion (I/R)mitochondriaPGC-1α |
| spellingShingle | Fei Lin Yu-Qing Tan Yu-Qing Tan Xuan-Hui He Li-Li Guo Ben-Jun Wei Jun-Ping Li Zhong Chen Heng-Wen Chen Jie Wang Huoxue Huatan Decoction Ameliorates Myocardial Ischemia/Reperfusion Injury in Hyperlipidemic Rats via PGC-1α–PPARα and PGC-1α–NRF1–mtTFA Pathways Frontiers in Pharmacology Huoxue Huatan Decoction hyperlipidemia ischemia/reperfusion (I/R) mitochondria PGC-1α |
| title | Huoxue Huatan Decoction Ameliorates Myocardial Ischemia/Reperfusion Injury in Hyperlipidemic Rats via PGC-1α–PPARα and PGC-1α–NRF1–mtTFA Pathways |
| title_full | Huoxue Huatan Decoction Ameliorates Myocardial Ischemia/Reperfusion Injury in Hyperlipidemic Rats via PGC-1α–PPARα and PGC-1α–NRF1–mtTFA Pathways |
| title_fullStr | Huoxue Huatan Decoction Ameliorates Myocardial Ischemia/Reperfusion Injury in Hyperlipidemic Rats via PGC-1α–PPARα and PGC-1α–NRF1–mtTFA Pathways |
| title_full_unstemmed | Huoxue Huatan Decoction Ameliorates Myocardial Ischemia/Reperfusion Injury in Hyperlipidemic Rats via PGC-1α–PPARα and PGC-1α–NRF1–mtTFA Pathways |
| title_short | Huoxue Huatan Decoction Ameliorates Myocardial Ischemia/Reperfusion Injury in Hyperlipidemic Rats via PGC-1α–PPARα and PGC-1α–NRF1–mtTFA Pathways |
| title_sort | huoxue huatan decoction ameliorates myocardial ischemia reperfusion injury in hyperlipidemic rats via pgc 1α pparα and pgc 1α nrf1 mttfa pathways |
| topic | Huoxue Huatan Decoction hyperlipidemia ischemia/reperfusion (I/R) mitochondria PGC-1α |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.546825/full |
| work_keys_str_mv | AT feilin huoxuehuatandecoctionamelioratesmyocardialischemiareperfusioninjuryinhyperlipidemicratsviapgc1apparaandpgc1anrf1mttfapathways AT yuqingtan huoxuehuatandecoctionamelioratesmyocardialischemiareperfusioninjuryinhyperlipidemicratsviapgc1apparaandpgc1anrf1mttfapathways AT yuqingtan huoxuehuatandecoctionamelioratesmyocardialischemiareperfusioninjuryinhyperlipidemicratsviapgc1apparaandpgc1anrf1mttfapathways AT xuanhuihe huoxuehuatandecoctionamelioratesmyocardialischemiareperfusioninjuryinhyperlipidemicratsviapgc1apparaandpgc1anrf1mttfapathways AT liliguo huoxuehuatandecoctionamelioratesmyocardialischemiareperfusioninjuryinhyperlipidemicratsviapgc1apparaandpgc1anrf1mttfapathways AT benjunwei huoxuehuatandecoctionamelioratesmyocardialischemiareperfusioninjuryinhyperlipidemicratsviapgc1apparaandpgc1anrf1mttfapathways AT junpingli huoxuehuatandecoctionamelioratesmyocardialischemiareperfusioninjuryinhyperlipidemicratsviapgc1apparaandpgc1anrf1mttfapathways AT zhongchen huoxuehuatandecoctionamelioratesmyocardialischemiareperfusioninjuryinhyperlipidemicratsviapgc1apparaandpgc1anrf1mttfapathways AT hengwenchen huoxuehuatandecoctionamelioratesmyocardialischemiareperfusioninjuryinhyperlipidemicratsviapgc1apparaandpgc1anrf1mttfapathways AT jiewang huoxuehuatandecoctionamelioratesmyocardialischemiareperfusioninjuryinhyperlipidemicratsviapgc1apparaandpgc1anrf1mttfapathways |