Effect of Ciprofol on Pyroptosis of Myocardial Cells in Mice with Myocardial Ischemia-reperfusion by Regulating the HMGB1-RAGE Signaling Pathway
JI Xiaoyan
HUANG Chunxia
ZHANG Jinchun
Abstract：Objective:To investigate the effect of ciprofol on pyroptosis of myocardial cells in myocardial ischemia-reperfusion(MIRI)mice by regulating the high mobility group box 1 protein(HMGB1)-receptor for advanced glycation end products(RAGE)signaling pathway.Methods:According to random number table method,the mice were divided into sham group,MIRI group,ciprofol group,positive control group(fasudil hydrochloride)and activator group(HMGB1-RAGE signaling pathway activator DEX),with 12 mice in each group.Except the sham group,the MIRI mouse model was established by ligation of the anterior descending branch of the left coronary artery,and each group was intraperitoneally injected with the corresponding drug once a day for 7 days before modeling.Serum myocardial injury markers of creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),creatine kinase(CK)and inflammatory factors interleukin(IL)-18,IL-1βand tumor necrosis factor(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin(HE)staining was used to observe the pathological damage of myocardial tissue.Myocardial cell apoptosis was detected by immunofluorescence staining.The expressions of NOD-like receptor protein 3(NLRP3)and apoptosis-associated speckle protein(ASC)were detected by immunohistochemistry.The expression of dermatin D(GSDMD),Cleaved Caspase-1,HMGB1,and RAGE in myocardial tissue were detected by Western Blot.Results:Compared with sham group,the levels of myocardial injury markers CK-MB,LDH,CK and inflammatory factor IL-18 in MIRI group,levels of IL-1 β,TNF-α,myocardial scorch death rate,NLRP3,ASC,GSDMD,Cleaved Caspase-1,HMGB1,RAGE expression levels significantly increased(P＜0.05).Compared with MIRI group,the levels of myocardial injury markers CK-MB,LDH,CK,inflammatory factor IL-18 in Ciprofol group and positive control group,levels of IL-1 β,TNF-α,myocardial scorching rate,NLRP3,ASC,GSDMD,Cleaved Caspase-1,HMGB1,RAGE expression levels significantly decreased(P＜0.05).Compared with the ciprofol group,the changes of the above indexes in the activator group were significantly reversed(P＜0.05).Conclusion:Ciprofol can effectively alleviate the injury of MIRI,the mechanism of which may be related to inhibiting the activation of HMGB1-RAGE pathway and thus inhibiting the pyrodeath of cardiomyocytes.
Keywords：myocardial ischemia-reperfusionpyroptosisciprofolhigh mobility group box 1 proteinHMGB1receptor for advanced glycation end productsRAGE
Publication Date：2025-05-10
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 1325-1330 )