Effect of postconditioning with α7 nicotinic acetylcholine receptor agonist on myocardial ischemia/reperfusion injury in rats with hypercholesterolemia
WEN Chao1, XUE Fushan2, WANG Yuhui1, JIN Jinhua1
1. Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100144, China; 2. Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
Abstract:Objective To evaluate the effect of postconditioning with α7 nicotinic acetylcholine receptor (α7nAChR) agonist on myocardial protection in hypercholesterolemic rats.Methods A hypercholesterolemic model of rats was induced by means of a eight-week diet containing 2% cholesterol and 0.5% bile salts. Hypercholesterolemic and normal rats were randomly divided into three groups respectively (n=5): control group (group HC and NC), ischemia/reperfusion injury group (group HI and NI), and PNU282987 postconditioning group (group HPNU and NPNU). Serum levels of total cholesterol (TC), low-density lipoprotein (LDL), creatine kinase MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor (TNF) -α and interleukin (IL) -6 were assayed. The size of myocardial infarction was determined by Evans blue and triphenyltetrazolium chloride (TTC) staining.Results Compared with group NC, levels of TC and LDL were elevated significantly in group HC (P<0.05). Compared with group NI, serum levels of CKMB, cTnI, TNF-α, IL-6, and myocardial infarct size were decreased significantly in group NPNU (P<0.05). No significant difference was found between group HI and group HPNU (P>0.05).Conclusions Hypercholesterolemia can aggravate myocardial ischemia/reperfusion injury and eliminate the myocardial protective effect of α7nAChR agonist postconditioning against myocardial ischemia/reperfusion injury.
Heusch G, Gersh B J. The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge[J]. Eur Heart J,2017,38(11):774-784.
[2]
Xiong J, Yuan Y J, Xue F S, et al. Postconditioning with α7nAChR agonist attenuates systemic inflammatory response to myocardial ischemia-reperfusion injury in rats[J]. Inflammation, 2012, 35 (4):1357-1364.
[3]
Andreadou I, Iliodromitis E K, Lazou A, et al. Effect of hypercholesterolaemia on myocardial function, ischaemia-reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning[J]. Br J Pharmacol, 2017,174(12):1555-1569.
[4]
Yang J T, Wang J, Zhou X R, et al. Luteolin alleviates cardiac ischemia/reperfusion injury in the hypercholesterolemic rat via activating Akt/Nrf2 signaling[J]. Naunyn Schmiedebergs Arch Pharmacol, 2018,391(7):719-728.
[5]
Chan K W, Ismail M, Mohd E N, et al. Defatted Kenaf (Hibiscus cannabinus L.) seed Meal and its phenolic-saponin-Rich Extract Protect Hypercholesterolemic Rats against oxidative stress and systemic Inflammation via Transcriptional Modulation of Hepatic Antioxidant Genes[J]. Oxid Med Cell Longev, 2018,2018:6742571.
[6]
Li H X, Cui X L, Xue F S, et al. Inhibition of glycogen synthase kinase-3β is involved in cardioprotection by α7nAChR agonist and limb remote ischemic postconditionings[J]. Biosci Rep, 2018,38(5): BSR20181315.
[7]
Liu Y Y, Sun C, Xue F S, et al. Effect of autophagy Inhibition on the protection of ischemia preconditioning against Myocardial Ischemia/Reperfusion Injury in Diabetic Rats[J]. Chin Med J (Engl),2018,131(14):1702-1709.
[8]
Blay R M, Adjenti S K, Adutwum-Ofosu K K, et al. Natural cocoa inhibits maternal hypercholesterolaemia-induced atherogenesis in rabbit pups[J]. Cardiovasc J Afr,2019,30(4):208-215.
[9]
Lin Z J, Zhang B, Liu X Q, et al. Abdominal fat accumulation with hyperuricemia and hypercholesterolemia quail model induced by high fat diet. Chin Med Sci J[J]. 2009, 24(3):191-194.
[10]
Chandra A, Sharma K, Pratap K, et al. Inhibition of microRNA-128-3p attenuates hypercholesterolemia in mouse model[J]. Life Sci,2021,264:118633.
[11]
Low LD, Lu L, Chan CY, et al. IL-13-driven alterations in hepatic cholesterol handling contributes to hypercholesterolemia in a rat model of minimal change disease[J]. Clin Sci (Lond),2020,134(2):225-237.
Low LD, Lu L, Chan C Y, et al. IL-13-driven alterations in hepatic cholesterol handling contributes to hypercholesterolemia in a rat model of minimal change disease[J]. Clin Sci (Lond) ,2020, 134(2):225-237.
[14]
Zhu J, Wang Y F, Chai X M, et al. Exogenous NADPH ameliorates myocardial ischemia-reperfusion injury in rats through activating AMPK/mTOR pathway[J]. Acta Pharmacol Sin, 2020,41(4):535-545.
[15]
Sharma N K, Mahadevan N, Balakumar P. Adenosine transport blockade restores attenuated cardioprotective effects of adenosine preconditioning in the isolated diabetic rat heart: potential crosstalk with opioid receptors[J]. Cardiovasc Toxicol, 2013,13(1):22-32.
Mazo T, D'Annunzio V, Donato M, et al. Dyslipidemia in Ischemia/Reperfusion Injury[J]. Adv Exp Med Biol, 2019,1127:117-130.
[18]
Ambrosio G, Tritto I. Reperfusion injury: experimental evidence and clinical implications[J]. Am Heart J, 1999,138: S69-75.
[19]
Steffens S, Montecucco F, Mach F. The inflammatory response as a target to reduce myocardial ischaemia and reperfusion injury[J]. Thromb Haemost, 2009,102(2):240-247.
[20]
Wu Y, Liu H, Wang X. Cardioprotection of pharmacological postconditioning on myocardial ischemia/reperfusion injury[J]. Life Sci, 2021,264:118628.