丁香酚对大鼠心肌缺血再灌注损伤的抑制作用及其机制  

Inhibitory effect of eugenol on myocardial ischemia-reperfusion injury in rats and its mechanism

作　　者：朱秋梦 石佳琦 吕玮 张昕 肖云峰 ZHU Qiumeng;SHI Jiaqi;LYV Wei;ZHANG Xin;XIAO Yunfeng(School of Pharmacy,Inner Mongolia Medical University,Hohhot 010110,China;不详)

机构地区：[1]内蒙古医科大学药学院,呼和浩特010110 [2]内蒙古医科大学新药安全评价研究中心

出　　处：《山东医药》2024年第5期7-11,共5页Shandong Medical Journal

基　　金：内蒙古自治区自然科学基金项目(2023MS08032);内蒙古自治区科技计划软科学项目(2022RKX0003)。

摘　　要：目的观察丁香酚对大鼠心肌缺血再灌注损伤(MIRI)的抑制作用并分析其机制。方法Wistar大鼠随机分为假手术组、MIRI组、丁香酚低剂量组、丁香酚中剂量组、丁香酚高剂量组、阳性对照组,每组10只。丁香酚低、中、高剂量组及阳性对照组分别给予50、100、200 mg/(kg·d)丁香酚及30 mg/(kg·d)盐酸地尔硫[艹卓]灌胃14 d,假手术组、MIRI组给予羧甲基纤维素钠溶液灌胃。除假手术组外,各组均于末次给药1 h后采用结扎冠状动脉左前降支法建立大鼠MIRI模型,假手术组开胸后在冠状动脉左前降支处仅穿线不结扎。采用全自动生化分析仪检测各组血清心肌损伤标志物肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH);摘取大鼠心脏,TTC染色后计算心肌梗死面积比。采用转录组测序筛选丁香酚作用于MIRI的差异表达基因,对转录组测序筛选出的差异表达基因进行GO功能及KEGG信号通路富集分析。结果血清心肌损伤标志物CK、CK-MB、LDH水平MIRI组>丁香酚低剂量组、丁香酚中剂量组、丁香酚高剂量组、阳性对照组>假手术组,心肌梗死面积比假手术组>丁香酚低剂量组、丁香酚中剂量组、丁香酚高剂量组、阳性对照组>MIRI组(P均<0.05)。与MIRI组比较,丁香酚低剂量组共有1035个差异表达基因,其中594个基因上调、441个基因下调;丁香酚中剂量组共有513个差异表达基因,其中197个基因上调、316个基因上调;丁香酚高剂量组共有1962个差异表达基因,其中1151个基因上调、811个基因下调。丁香酚各剂量组与MIRI组差异表达基因的GO分析结果显示,丁香酚作用于MIRI的生物过程主要涉及免疫反应、氧气输送、急性期反应等;细胞组分主要涉及细胞外空间、染色体、细胞外基质等;分子功能主要涉及趋化因子的活动、载氧活性、钙离子结合等。丁香酚各剂量组与MIRI组差异表达基因的KEGG分析结果显示,丁�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 eugenol 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 myocardial 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-triphenyltetrazolium 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)function 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,mediumdose eugenol group,high-dose eugenol group,and positive control group>sham operation group,and the myocardial infarction 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

关 键 词：丁香酚 心肌缺血再灌注损伤 转录组学 HIF-1信号通路 

分 类 号：R966[医药卫生—药理学]