Inhibitory effect of eugenol on myocardial ischemia-reperfusion injury in rats and its mechanism
Objective To investigate the inhibitory effect of eugenol on myocardial ischemia-reperfusion injury(MIRI)in rats and to analyze its mechanism.Methods Wistar rats were randomly divided into sham operation group,MIRI model group,low-dose eugenol group,medium-dose eugenol group,high-dose eugenol group,and positive control group,with 10 rats in each group.Rats in the low-dose eugenol group,medium-dose eugenol group,and high-dose euge-nol group were given 50,100,and 200 mg/(kg·d)eugenol and 30 mg/(kg·d)diltiazepine hydrochloride by gavage for 14 d,respectively,while rats in the sham operation group and MIRI model group were given sodium carboxymethyl cellulose(CMC-Na)solution by gavage.MIRI models were established 1 h after the last administration by ligation of the left anterior descending branch of coronary artery in all groups,except the sham operation group.The left anterior descending branch of coronary artery was only lapped without ligation in sham operation group after chest opening.Serum markers of myocardi-al injury,such as creatine kinase(CK),creatine kinase isoenzyme(CK-MB),and lactate dehydrogenase(LDH),were detected by automatic biochemical analyzer.The myocardial infarction area ratio was calculated by 2,3,5-triphenyltetrazo-lium chloride(TTC)staining after heart extraction.The differentially expressed genes of MIRI induced by eugenol were screened by transcriptome sequencing.The screened differentially expressed genes underwent Gene ontology(GO)func-tion and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis.Results Serum myocardial injury markers CK,CK-MB,and LDH levels were as follows:MIRI group>low-dose eugenol group,medium-dose eugenol group,high-dose eugenol group,and positive control group>sham operation group,and the myocardial in-farction area ratio was in the following order:sham-operation group>low-dose eugenol group,medium-dose eugenol group,high-dose eugenol group,and positive control group>MIRI group(all P<0.05).Compared with the MIRI group,there were a total of 1 035 differentially expressed genes in the low-dose eugenol group,of which 594 genes were up-regu-lated and 441 genes were down-regulated;there were a total of 513 differentially expressed genes in the medium-dose euge-nol group,of which 197 genes were up-regulated and 316 genes were up-regulated;and there were a total of 1 962 differen-tially expressed genes in the high-dose eugenol group,of which 1 151 genes were up-regulated and 811 genes were down-regulation.GO analysis of the differentially expressed genes in the eugenol dose groups and the MIRI group showed that the biological processes of eugenol in MIRI were mainly related to immune response,oxygen transport,acute phase re-sponse pairs,etc.;the cellular components were mainly related to the extracellular space,chromosomes,and extracellu-lar matrix,etc.;and the molecular functions were mainly related to the activities of chemokines,oxygen-carrying activity,and calcium-ion binding,etc.KEGG analysis of the differentially expressed genes in the eugenol dose groups and the MIRI group showed that the differentially expressed genes under the action of eugenol were mainly involved in signaling pathways such as the forkhead box O(FOXO)signaling pathway,hypoxia inducible factor-1(HIF-1)signaling pathway,PI3K-AKT signaling pathway,and JAK-STAT signaling pathway and other signaling pathways;among them,the HIF-1 signaling pathway had the highest enrichment score and the most significant difference.Conclusion Eugenol can inhibit the MIRI of rats,and its molecular mechanism may be related to regulating the HIF-1 signaling pathway.
万方数据
维普
