Effects of Remimazolam on Cardiomyocytes Pyroptosis in Rats with Myocardial Ischemia-reperfusion Injury by Regulating HMGB1-RAGE Signaling Pathway
Objective To investigate the effects of remimazolam on cardiomyocytes pyroptosis in rats with myocar-dial ischemia-reperfusion injury(MI/RI)by regulating high mobility group protein B1(HMGB1)-receptor for advanced glycation end products(RAGE)signaling pathway.Methods 50 SD male rats were divided into sham operation group,model group and remazolam low-dose group(5 mg/kg remimazolam),remazolam high-dose group(10 mg/kg remimazo-lam),remazolam high-dose+rHMGB1 group(5 mg/kg remimazolam+8 μg/kg rHMGB1)according to random number table method,with 10 rats in each.The pathological changes of myocardial tissue in rats were observed by hematoxylin-e-osin(HE)staining;the ultrastructure of myocardial tissue was observed with the transmission electron microscope;the expression of N-terminal fragment of gas-dermin D(GSDMD-N)in myocardial tissue was detected by immunohistochemistry;the area of myocardial infarction was detected by tetrazolium red staining;the levels of lactate dehydrogenase(LDH),interleukin 1 beta(IL-1β),interleukin-18(IL-18)and interleukin-10(IL-10)in serum were de-tected by enzyme-linked immunosorbent assay;the content of malondialdehyde(MDA)in myocardial tissue was deter-mined by thiobarbituric acid method;superoxide dismutase(SOD)was determined by hydroxylamine method;glutathione peroxidase(GSH-Px)activity was determined by colorimetric method;the protein levels of nucleotide-binding oligomer-ization domain-like receptor protein 3(NLRP3),cysteinyl aspartate specific proteinase 1(caspase-1),GSDMD-N,HMGB1,RAGE,nuclear factor κB(NF-κB)and phosphorylated-nuclear factor κB(p-NF-KB)in myocardial tissue were detected by Western blot method.Results Compared with sham operation group,the myocardial tissue was significantly damaged,the percentage of myocardial infarction area,serum LDH,IL-1β,IL-18 levels,MDA content in myocardial tis-sue,NLRP3,caspase-1,GSDMD-N,HMGB1,RAGE,p-NF-κB/NF-κB protein expression were significantly increased(all P＜0.05),serum IL-10 level,SOD and GSH-Px activity in myocardial tissue were significantly decreased in model group(all P＜0.05);compared with model group,the myocardial tissue injury was significantly reduced,the percentage of myocardial infarction area,serum LDH,IL-1β,IL-18 levels,MDA content in myocardial tissue,NLRP3,caspase-1,GSDMD-N,HMGB1,RAGE,p-NF-κB/NF-κB protein expression were significantly decreased,serum IL-10 level,SOD and GSH-Px activity in myocardial tissue were significantly increased in remazolam low-dose group and remazolam high-dose group(all P＜0.05);compared with remazolam low-dose group,the myocardial tissue injury was significantly re-duced,serum LDH,IL-1β,IL-18 levels,MDA content in myocardial tissue,NLRP3,caspase-1,GSDMD-N,HMGB1,RAGE,p-NF-κB/NF-κB protein expression were significantly decreased(all P＜0.05),serum IL-10 level,SOD and GSH-Px activity in myocardial tissue were significantly increased in remazolam high-dose+rHMGB1 group(all P＜0.05).Conclusion Remimazolam may reduce cardiomyocytes pyroptosis in MI/RI rats by inhibiting HMGB1-RAGE sig-naling pathway,reducing inflammatory response and oxidative stress,thereby improving myocardial injury.
RemimazolamHigh mobility group protein B1Receptor for advanced glycation end productsSigna-ling pathwayMyocardial ischemia-reperfusion injuryCardiomyocytesPyroptosisInflammationOxidative stress
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