中国药房2024，Vol.35Issue(8)：955-960,6.DOI:10.6039/j.issn.1001-0408.2024.08.10
阿芬太尼调节SphK1/S1P信号通路对急性心肌梗死大鼠心肌纤维化的影响
Effects of alfentanil on myocardial fibrosis in rats with acute myocardial infarction by regulating the SphK1/S1P signaling pathway
摘要
Abstract
OBJECTIVE To explore the effects of alfentanil(ALF)on myocardial fibrosis in rats with acute myocardial infarction(AMI)by regulating sphingosine kinase 1(SphK1)/sphingosine 1-phosphate(S1P)signaling pathway.METHODS Male SD rats were collected to construct AMI model by the ligation of anterior descending branch of left coronary artery.The successfully modeled rats were randomly divided into AMI model group(Model group),ALF low-dose group(ALF-L group,0.25 mg/kg ALF),ALF high-dose group(ALF-H group,0.5 mg/kg ALF),high dose of ALF+SphK1 activator group(ALF-H+K6PC-5 group,0.5 mg/kg ALF+1 μg/g K6PC-5).At the same time,a sham operation group(Sham group)was set up to perform only chest opening/closing operations without ligating the anterior descending branch of left coronary artery,with 15 rats in each group.Rats in each drug group were intraperitoneally injected with the corresponding drug solution,once a day,for 4 consecutive weeks.Twelve hours after the last medication,cardiac function indicators[left ventricular systolic pressure(LVSP),left ventricular ejection fraction(LVEF),left ventricular systolic diameter(LVSD),left ventricular fractional shortening(LVFS)]of rats were detected in each group;the condition of myocardial infarction,pathological changes in myocardial tissue,and degree of fibrosis were observed;serum levels of brain natriuretic peptide(BNP)and cardiac troponin Ⅰ(cTnⅠ)in rats were detected.The protein expressions of collagen Ⅰ,collagen Ⅲ,matrix metalloproteinase-2(MMP-2),SphK1 and S1P were also detected in the myocardial tissue of rats.RESULTS Compared with the Sham group,the arrangement of myocardial cells in the Model group was disordered,with a large number of inflammatory cells infiltrating.The levels of LVSP,LVFS and LVEF in the Model group were significantly reduced(P＜0.05);LVSD level,myocardial infarction area,collagen volume fraction,serum levels of BNP and cTnⅠ,the protein expressions of collagen Ⅰ,collagen Ⅲ,MMP-2,SphK1 and S1P in myocardial tissue were significantly increased or enlarged(P＜0.05).Compared with the Model group,the pathological changes and degree of fibrosis in the myocardial tissue of rats in each dose group of ALF were improved or relieved,while the quantitative indicators of rats in the ALF-H group were significantly improved and significantly better than those in ALF-L group(P＜0.05).K6PC-5 could significantly reverse the improvement effect of high-dose ALF on the above quantitative indicators in rats(P＜0.05).CONCLUSIONS ALF can reduce myocardial fibrosis and improve cardiac function in AMI rats,and the effect may be related to the inhibition of the SphK1/S1P signaling pathway.关键词
阿芬太尼/急性心肌梗死/心肌纤维化/SphK1/S1P信号通路Key words
alfentanil/acute myocardial infarction/myocardial fibrosis/SphK1/S1P signaling pathway分类
医药卫生引用本文复制引用
肖锦亮,邹雪,但家朋..阿芬太尼调节SphK1/S1P信号通路对急性心肌梗死大鼠心肌纤维化的影响[J].中国药房,2024,35(8):955-960,6.基金项目
荆州市2020年度医疗卫生科技计划项目(No.2020HC05) （No.2020HC05）
