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作 者:郎勇 冉迅[1] 屈模英[1] LANG Yong;RAN Xun;QU Moying(Department of Cardiology,Shangjin Hospital,West China Hospital,Sichuan University,Chengdu,610000,China)
机构地区:[1]四川大学华西医院上锦医院心内科,成都市610000
出 处:《医学分子生物学杂志》2020年第2期91-96,108,共7页Journal of Medical Molecular Biology
基 金:资助项目:四川省卫生和计划生育委员会科研课题(No.16PJ305)。
摘 要:目的探索蒿本内酯对心肌缺血再灌注(MIRI)大鼠心肌损伤的影响。方法60只SD大鼠随机分为对照组、I/R组、阳性对照组(地尔硫卓,5 mg/kg)、蒿本内酯组低中高剂量组(10、20、40 mg/kg)。造模后,超声心动图检查LVEF、FS和LVWT;ELISA检测血清CK-MB、Mb、cTnI、IL-18、IL-1β、IL-6、MCP-1和TNF-α;检测Caspase-3、ATG7、LC3Ⅱ/LC3Ⅰ、p62、PI3K/AKT/mTOR通路表达。结果与I/R组比,蒿本内酯高剂量组大鼠HR、LVSP、LVWT、LVEF、FS升高,血清CK-MB、Mb、cTnI、IL-18、IL-1β、IL-6、MCP-1和TNF-α下降(P<0.05);心肌组织中ATG7、LC3Ⅱ/LC3Ⅰ、Caspase-3、p-PI3K/PI3K、p-AKT/AKT、p-mTOR/mTOR表达下调(P<0.05),p62表达上调(P<0.05)。结论蒿本内酯可能通过抑制PI3K/AKT/mTOR的磷酸化,改善MIRI心肌组织损伤。Objective To investigate the effects of ligustilide on myocardial injury in rats with myocardial ischemia reperfusion injury(MIRI).Methods Sixty SD rats were randomly divided in-to control group,ischemia/reperfusion(I/R)group,positive control group(diltiazem,5 mg/kg),and low-dose,medium-dose and high-dose ligustilide groups(10 mg/kg,20 mg/kg,40 mg/kg).After modeling,LVEF,FS and LVWT were examined by echocardiography.The levels of CK-MB,Mb,cTnI,IL-18,IL-1β,IL-6,MCP-1 and TNF-αin the serum were measured by ELISA.The expression levels of caspase-3,ATG7,LC3Ⅱ/LC3Ⅰ,p62 and PI3K/AKT/mTOR pathways were detected.Results In high-dose ligustilide group,HR,LVSP,LVWT,LVEF and FS were significantly increased(P<0.05),the levels of serum CK-MB,Mb,cTnI,IL-18,IL-1β,IL-6,MCP-1 and TNF-αwere markedly decreased(P<0.05),the expression of ATG7 and、LC3Ⅱ/LC3Ⅰ,caspase-3,p-PI3K/PI3K,p-AKT/AKT and p-mTOR/mTOR in myocardial tissues was profoundly down-regulated(P<0.05),and the expression of p62 was obviously up-regulated(P<0.05).There were significant differences in these indexes between high-dose ligusti-lide group and I/R group.Conclusion Ligustilide may improve myocardial tissue damage in MIRI by inhibiting the phosphorylation of PI3K/AKT/mTOR.
关 键 词:心肌缺血再灌注 蒿本内酯 PI3K/AKT/MTOR
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