Remifentanil protects heart from myocardial ischaemia/reperfusion (I/R) injury via miR-206-3p/TLR4/NF-κB signalling axis

Abstract

Objectives Myocardial I/R injury is one of the most serious complications after reperfusion therapy in patients with myocardial infarction. Remifentanil has been found to protect the heart against I/R injury. However, its underlying mechanism remains uncertain in myocardial I/R injury. Methods The myocardial I/R injury rat model was established by 30 min of ischaemia followed by 24 h of reperfusion. The animal model was evaluated by the levels of TC, ALT and AST and H&E staining. The binding of miR-206-3p and TLR4 was predicted and verified using TargetScan software, luciferase reporter and RNA pull-down assays. The functional role and mechanism of remifentanil were identified by ultrasonic echocardiography, oxidative stress markers, H&E, Masson and TUNEL staining and western blot. Key findings The rat myocardial I/R injury model displayed a significantly high level of TC, ALT, AST, TLR4, p-IκBα and p-p65 and the presence of disorganized cells and inflammatory cell infiltration. The model also showed increased levels of LVEDD, LVESD, MDA, fibrosis and apoptosis and decreased levels of EF, FS, SOD and GSH, which were reversed with remifentanil treatment. Knockdown of miR-206-3p damaged cardiac function and aggravated oxidative stress. miR-206-3p could directly bind to TLR4. TLR4 overexpression destroyed cardiac function, exacerbated oxidative stress, increased levels of p-IκBα and p-p65 and aggravated pathology manifestation affected by remifentanil. Conclusions Our results elucidated that remifentanil alleviated myocardial I/R injury by miR-206-3p/TLR4/NF-κB signalling axis.

miR-206 alleviates LPS-induced inflammatory injury in cardiomyocytes via directly targeting USP33 to inhibit the JAK2/STAT3 signaling pathway

“…Yang et al also showed that miR-206 contributed to cardiomyocyte hypertrophy and survival by regulating YAP [ 25 ]. Moreover, Zhang et al's also highlighted that a decrease in miR-206 could impair cardiac function and promote oxidative stress by removing the inhibitory role of TLR4[ 26 ]. These data implied that miR-206 was most likely a heart-protective factor.…”

miRNA-206-3p alleviates LPS-induced acute lung injury via inhibiting inflammation and pyroptosis through modulating TLR4/NF-κB/NLRP3 pathway

“…For example, Zhang et al found that remifentanil protected myocardial I/R injury by modulating the TLR4/NF-κB signaling pathway. Simultaneously, they found that the defense mechanism involved miRNA-206-3p, which plays a significant role in downregulating the expression of TLR4 45 . Therefore, in the current study, we sought to ascertain the potential protective function of miRNA-206-3p against LPS-induced ALI www.nature.com/scientificreports/ by specifically targeting TLR4.…”

“…Dong et al reported a protective role for miRNA-206 against myocardial inflammatory injuries induced by targeting the USP33, which may be a reliable therapeutic target 43 . Meanwhile, Zhou et al found that the effects of miRNA-206-3p on connexin, ultimately improving lung permeability in sepsis-induced ALI 44 .Some widely used medications, including remifentanil, protect the heart against the damage caused by myocardial ischemia/ reperfusion (I/R) by modulating the miRNA-206-3p 45 .…”

TRIM38 protects H9c2 cells from hypoxia/reoxygenation injury via the TRAF6/TAK1/NF-κB signalling pathway

“…The NF- κ B family plays a critical role in numerous biological processes, including apoptosis and inflammatory responses ( Karin & Greten, 2005 ; Courtois & Gilmore, 2006 ). When cardiomyocytes are stimulated by various chemical and mechanical signals, such as I/R, NF- κ B is activated ( Xiong et al, 2021 ; Zhang et al, 2022 ). Therefore, we investigated the effect of TRIM38 on NF- κ B signalling.…”