AIM To investigate the impacts of Yangxin decoction on cardiac function, myocardial injury, and autophagy in rats with ventricular remodeling after acute myocardial infarction (AMI) based on the adenosine monophosphate activated protein kinase (AMPK)/Unc-51-like kinase 1 (ULK1) signaling pathway.
METHODS Rats were randomized into (12 rats/group) sham surgery group, model group, Yangxin decoction group (12.07 g/(kg·d)), positive control group (sacubitril valsartan), and inhibitor group (Compound C, AMPK/ULK1 signaling pathway inhibitor). Except for the sham surgery group, the remaining groups were used to replicate the AMI rat model by ligating the anterior descending branch of the left coronary artery, while the sham surgery group was not subjected to ligation. Ultrasound echocardiography was applied to detect rat cardiac function. ELISA method was employed to detect the levels of serum lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), and angiotensin II (Ang II) in rats. HE and Masson staining were utilized to observe pathological damage in myocardial tissue. TUNEL staining was applied to observe myocardial cell apoptosis. Transmission electron microscopy was applied to observe the mitochondrial ultrastructure of myocardial tissue. Western blot was applied to detect the expression of microtubule associated protein 1 light chain 3I, 3II (LC3I, LC3II), selective autophagy junction protein 1 (P62), and AMPK/ULK1 signaling pathway related proteins in myocardial tissue.
RESULTS Compared with the sham surgery group, the model group demonstrated significant myocardial changes including myocardial fiber rupture, swelling, inflammatory cell infiltration, and collagen fiber deposition in cells. Additionally, the mitochondrial spine was broken and swollen, and the number decreased in the model group. The mean mitochondrial cross-sectional area, LVEF, LVFS, expression of LC3 Ⅱ/LC3 Ⅰ, p-AMPK/AMPK, and p-ULK1/ULK1 were all reduced, while the LDH, CK-MB, Ang II, myocardial tissue pathological score, myocardial fibrotic area, mean mitochondrial number, myocardial cell apoptosis rate, and expression of P62 elevated (all P<0.05). Compared with the model group, mean mitochondrial cross-sectional area, LVEF, LVFS, expression of LC3 Ⅱ/LC3 Ⅰ, p-AMPK/AMPK, and p-ULK1/ULK1 in the Yangxin decoction group and positive control group increased. Conversely, the LDH, CK-MB, Ang II, myocardial tissue pathological score, myocardial fibrotic area, mean mitochondrial number, myocardial cell apoptosis rate, and expression of P62 were reduced (all P<0.05). Compound C was found to weaken the promoting effect of Yangxin decoction on autophagy and aggravate myocardial injury after AMI (P<0.05).
CONCLUSION Yangxin decoction improves cardiac function and reduces myocardial injury in AMI rats, and its mechanism may be related to the activation of the AMPK/ULK1 signaling pathway and promotion of autophagy.
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