Mechanism of omege-6 PUFA increasing the susceptibility to acute myocardial ischemia injury
10.16438/j.0513-4870.2022-0353
- VernacularTitle:Omega-6型多不饱和脂肪酸增加急性心肌缺血损伤“易感性”的机制研究
- Author:
Jiang-han-zi LIU
1
;
Xiao-hui MA
2
;
Tian-hui YUAN
3
;
Wan-yang SUN
1
;
Yi-fang LI
1
;
Kurihara HIROSHI
1
;
Rong-rong HE
1
Author Information
1. Guangdong Engineering Research Center of Chinese Medicine and Disease Susceptibility, Jinan University, Guangzhou 510632, China; Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China; Guangdong Provincial Key Laboratory of Pharmacodynamic Substances of Traditional Chinese Medicine and Innovative Drugs, Jinan University, Guangzhou 510632, China
2. Guangdong Engineering Research Center of Chinese Medicine and Disease Susceptibility, Jinan University, Guangzhou 510632, China; Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China; Guangdong Provincial Key Laboratory of Pharmacodynamic Substances of Traditional Chinese Medicine and Innovative Drugs, Jinan University, Guangzhou 510632, China; Institute of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi 830054, China
3. The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China
- Publication Type:Research Article
- Keywords:
unsaturated fatty acid;
myocardial ischemia;
susceptibility;
arachidonic acid 12/15-lipoxygenase;
lipid peroxidation
- From:
Acta Pharmaceutica Sinica
2022;57(6):1657-1663
- CountryChina
- Language:Chinese
-
Abstract:
The abnormal lipids metabolism is a critical pathological feature of coronary heart disease (CHD). Additional supplemental intake of polyunsaturated fatty acid (PUFA) has long been considered to be an effective strategy for preventing CHD, but more and more clinical trials have denied this view. Still, it is ambiguity for the specific mechanism of PUFA in CHD. The experimental programs are compliant with ethical principles for animal use and have been approved by the Animal Experiment Ethics Committee of Jinan University. In the present study, we established an animal model by intake of omega-6 PUFA combined acute myocardial ischemia to explore the mechanism of CHD. Intragastric administration of linoleic acid (LA) for 14 days, intraperitoneal injection of isoprenaline (ISO) was applied to induce acute myocardial ischemia for the animal model establishment. The animal ultrasound imaging system was used to detect cardiac function in vivo after ISO injection for 24 h. Serum and heart tissue samples were collected for the myocardial enzyme, phospholipidomics analysis and molecular biological detection. Compared to the LA group, the cardiac function showed that the left ventricular ejection fraction (EF%) and the left ventricular shortening fraction (FS%) decreased, aspaetate aminotransferase (AST), creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH) increased in the LA + ISO mice. Compared to the ISO group, the phospholipidomics analysis showed that the PUFAs significantly were raised in the LA + ISO myocardium, and the content of oxidized phosphatidylethanolamine (ox-PE) changed most remarkable. Compared with the ISO group, the molecular biology detection showed that glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) were depleted, the end-products of ox-PE were increased, and the level of arachidonic acid 12/15-lipoxygenase (ALOX15) protein expression increased obviously. We suggest that ALOX15 mediated phospholipid peroxidation might be the critical mechanism of LA increased the susceptibility of myocardial ischemia injury. This study provides an experimental basis for whether PUFA could be used as an alternative treatment strategy for CHD prevention and provides a new intervention target for the early prevention strategy of CHD.
