AMPK activation can inhibit rapamycin (mTOR) via the mammalian target and, thus, triggers autophagy

AMPK activation can inhibit rapamycin (mTOR) via the mammalian target and, thus, triggers autophagy. appears to include suppression of autophagy via inhibiting AMPK/mTOR signalling, suggesting that YXK may serve as a potentially effective Chinese herbal compound for Implitapide suppressing Implitapide cardiac fibrosis in heart injury. strong class=”kwd-title” Keywords: Acute myocardial infarction, heart injury, cardiac fibrosis, Chinese herbal compound Introduction Acute myocardial infarction Rabbit polyclonal to PPP1CB (AMI)-induced heart Implitapide failure is one of the most frequently occurring heart diseases, and it contributes to high mortality in the world. Generally, myocardial infarction (MI) is the result of coronary arterial occlusion. MI leads to myocardial remodelling of the left ventricle, presenting as heart cavity dilatation, poor cardiac performance, arrhythmias, and even heart failure. A great number of factors are involved in cardiac remodelling post-MI, including myocardial cell death, apoptosis, and inflammation (Talman and Ruskoaho 2016). However, the process of pathological alteration of heart after MI is complicated, and it requires further study of novel targets and drug development for the treatment of MI. Autophagy is a natural process where long-lived proteins and damaged organelles are degraded and recycled, resulting in the turnover of long-lived proteins and damaged organelles (Mizushima and Komatsu 2011). Autophagy includes the following three different processes: macroautophagy, microautophagy, and chaperone-mediated autophagy. In this study, we focus on macroautophagy, which is generally referred to as autophagy. A defect in the autophagic process can promote cell apoptosis and cell death (Thorburn 2008). Autophagy was reportedly enhanced by MI and exerted protective effects on cardiac fibrosis and cardiac function (Wu et?al. 2014). In contrast, emerging evidence suggests that autophagy is detrimental under certain circumstances. Researchers have found that excessive autophagy could promote cardiomyocyte death during reperfusion (Matsui et?al. 2007), which likely occurred through the destroying of a large fraction of organelles (Zhu et?al. 2007). Moreover, the suppression of autophagy could reduce MI sizes (Wang et?al. 2015). Therefore, the role of autophagy in MI remains controversial. AMP-activated protein kinase (AMPK), a serine-threonine kinase, is important for maintaining energy homeostasis during cellular stress. AMPK activation can inhibit rapamycin (mTOR) via the mammalian target and, thus, triggers autophagy. AMPK-mTOR signalling plays a crucial role in cardiac function post-MI (Qi and Young 2015). Chinese medicine is widely used in clinical treatments in countries of Southeast Asia, including chronic heart failure, angina, and MI. Yangxinkang tablet (YXK) is a Chinese herbal compound, primarily comprising of ginseng, astragalus, radix ophiopogonis, schisandra, and pubescent holly root. Our previous studies (Peihua Ren et?al. 2018a, 2018b) showed that treatment with YXK improved cardiac function in rabbits post-MI. Here, we continue to study the effects of YXK on cardiac remodelling in a rat model post-MI and the relevant underlying mechanisms. Materials and methods MI model and experimental protocols Animal experiments were approved by the Institutional Animal Care and Use Committee at The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. The animals were treated in accordance with the Guide for the Care and Use of Laboratory Animals (8th edition, National Academies Press). Wistar rats (250?g, 7C8?weeks old) were obtained from Medical Experimental Animal Centre of Guangdong Province, Guangzhou, China. The MI model was created in accordance with a modified method in previous study (Wu et?al. 2011). Briefly, animals were anesthetized (by 5?mL/kg of 1% pentobarbital, i.p.) and artificially ventilated using a respirator. Next, the thorax was opened at the left third intercostal space, and MI was induced by ligating the proximal left anterior descending (LAD) coronary artery. The successful infarction was identified by visually observing a change of the colour of the anterior wall of the left ventricle from red to blanching and cyanosis and swelling of the left atrium. Animals in the sham group were subjected to the same surgical procedure but excluding the ligation LAD coronary artery. Rats were randomly assigned to five groups as follows: sham group (Sham, em n /em ?=?6); MI group, MI rats administered saline alone ( em n /em ?=?10); AICAR group (AMPK agonist), MI rats treated with AICAR (50?mg/kg, i.p., em n /em ?=?10) (Robert et?al. 2009); Com C group, MI rats treated with Compound C (10?mg/kg, i.p., em n /em ?=?10) (Abdulrahman et?al. 2014); YXK group, MI rats treated with YXK solution (0.72?g/kg/d, gavage, em n /em ?=?10). All the treatments were provided one day after the induction of MI. They were provided once a day and continued for four weeks post-MI. AICAR and Compound.