Restoration of autophagic flux in myocardial tissues is required for cardioprotection of sevoflurane postconditioning in rats

Abstract

Aim: Sevoflurane postconditioning (SpostC) has been shown to protect the heart from ischemia-reperfusion (I/R) injury. In this study, we examined whether SpostC affected autophagic flux in myocardial tissues that contributed to its cardioprotective effects in rats following acute I/R injury. Methods: SD rats underwent 30 min of left anterior descending coronary artery ligation followed by 120 min of reperfusion. The rats were subjected to inhalation of 2.4% (v/v) sevoflurane during the first 5 min of reperfusion, and chloroquine (10 mg/kg, ip) was injected 1 h before I/R. Myocardial infarct size was estimated using TTC staining. Autophagosomes in myocardial tissues were detected under TEM. Expression of LC3B-II, beclin-1, p62/SQSTM1, cathepsin B, caspase-3 and cleaved PARP was assessed using Western blot analysis. Plasma cardiac troponin I was measured using ELISA. Cardiomyocyte apoptosis was evaluated with TUNEL staining. Results: I/R procedure produced severe myocardium infarct and apoptosis accompanied by markedly increased number of autophagosomes, as well as increased levels of LC3B-II, beclin-1 and p62 in myocardial tissues. SpostC significantly reduced infarct size, attenuated myocardial apoptosis, restored intact autophagic flux and improved the lysosomal function in myocardial tissues. Administration of chloroquine that blocked autophagic flux abrogated the cardioprotective effects of SpostC. Conclusion: SpostC exerts its cardioprotective effects in rats following I/R injury via restoring autophagic flux in myocardial tissues.

Hydrogen sulfide protects against myocardial ischemia and reperfusion injury by activating AMP-activated protein kinase to restore autophagic flux

“…The dose and administration route for ADT were chosen based on our previous publication, which showed that intraperitoneally administered ADT at 50 mg/kg conferred robust protection in a well-established mouse model of cerebral ischemia [6]. In addition, it has been reported that compound c at 250 mg/kg abolishes cardioprotection conferred by AMPK activators [13] and that CQ at 10 mg/kg blocks the autophagy flux following myocardial I/R [11,14].…”

“…ROS likely accounts for beclin-1 upregulation and LAMP-2 down-regulation induced by I/R [11,14]. We used DHE to measure ROS generation as previously described [15].…”

Myocardial autophagic energy stress responses—macroautophagy, mitophagy, and glycophagy

“…In a Langendorff model of ischemia/reperfusion, inhibition of autophagy with the cell-permeable inhibitor (TATAtg5K130R) neither increased nor reduced infarct size, suggesting that in the absence of pre-or post-conditioning, the beneficial and deleterious effects of autophagy may be balanced (34). Inhibition of autophagic flux increases hypoxia/ reoxygenation injury (109) and blocks the beneficial effects of sevoflurane postconditioning (107). Ischemia/reperfusion injury disrupts autophagosome-lysosome fusion (54), accompanied by a significant increase in Beclin-1.…”

Remote Ischaemic Preconditioning and Sevoflurane Postconditioning Synergistically Protect Rats from Myocardial Injury Induced by Ischemia and Reperfusion Partly via Inhibition TLR4/MyD88/NF-κB Signaling Pathway

“…I/R injury decreases myocardial cell viability, causes cardiac dysfunction, may have a life-threatening consequence [1]. Different conditioning strategies is proved to be effective for prevention of I/R injury in animal models [1,2].…”