舒芬太尼通过调节HIF-1α-Kcnq1ot1影响缺氧-复氧导致的心肌细胞损伤  

Sufentanil protects against hypoxia-reoxygenation-induced myocardialcell injury by regulating HIF-1α- Kcnq1ot1

作　　者：邓方方[1] 李继勇[1] 张力[1] 邹高锐 陈治军 辛欢 乐薇[2] Deng Fang-fang;Li Ji-yong;ZHANG Li;Zou Gao-rui;Chen Zhi-jun;XIN Huan;Le Wei(Dept of Anesthesia,Wuhan First Hospital,Wuhan 430022,China;Dept of Acupuncture and Moxibustion,Wuhan First Hospital,Wuhan 430022,China)

机构地区：[1]武汉市第一医院麻醉科,湖北武汉430022 [2]武汉市第一医院针灸科,湖北武汉430022

出　　处：《中国药理学通报》2025年第3期500-507,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82071247);武汉市医学科研项目(No WX21D26)。

摘　　要：目的探讨舒芬太尼(sufentanil,Suf)能否通过调节缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)-KCNQ1重叠转录物1(KCNQ1 opposite strand/antisense transcript 1,Kcnq1ot1)改善缺氧-复氧(hypoxia-reoxygenation,H/R)导致的心肌细胞损伤。方法生物信息学分析预测HIF-1α与Kcnq1ot1的相互作用。将H9c2细胞分为Ctrl组、H/R组、Suf组;oe-HIF-1α组、oe-HIF-1α+Suf组、sh-HIF-1α组、sh-HIF-1α+Kcnq1ot1组。MTT法检测细胞活性,TUNEL法检测细胞凋亡,ELISA法检测细胞上清液中的CK-MB与HBDH浓度,Western blot分析细胞中HIF-1α蛋白表达,逆转录定量PCR(RT-qPCR)测定Kcnq1ot1的mRNA表达水平。构建心肌缺血/再灌注大鼠模型,评估Suf对体内心肌缺血/再灌注的治疗潜力。结果生物信息学分析发现,HIF-1α与Kcnq1ot1之间存在直接的相互作用。与Ctrl组相比,H/R组的H9c2细胞活性降低,细胞凋亡增加,CK-MB与HBDH浓度上调,HIF-1α与Kcnq1ot1的表达增强(均P<0.05)。转染oe-HIF-1α后,进一步加剧了上述结果(均P<0.05);而Suf干预抑制了以上结果(均P<0.05)。与H/R组相比,sh-HIF-1α组的细胞活性明显改善,凋亡减少,CK-MB与HBDH浓度降低(均P<0.05);转染Kcnq1ot1则部分逆转了这些结果(均P<0.05)。动物实验发现,Suf能够改善大鼠心肌缺血/再灌注损伤。结论Suf通过抑制HIF-1α-Kcnq1ot1改善心肌H/R损伤。Aim To investigate the mechanism by which sufentanil(Suf)improved hypoxia-reoxygenation(H/R)-induced myocardial cell injury by regulating hypoxia inducible factor-1α(HIF-1α)and KCNQ1 opposite strand/antisense transcript 1(Kcnq1ot1).Methods Bioinformatics analysis was conducted to predict the interaction between HIF-1αand Kcnq1ot1.Subsequently,H9c2 cells were divided into multiple treatment groups:Ctrl group,H/R group,and Suf group.Further grouping was based on different transfection conditions,including oe-HIF-1αgroup,oe-HIF-1α+Suf group,sh-HIF-1αgroup,and sh-HIF-1α+Kcnq1ot1 group.Cell viability was detected using the MTT assay,cell apoptosis was detected using the TUNEL assay,and the concentrations of CK-MB and HBDH in cell supernatants were measured using ELISA.HIF-1αprotein expression in cellswas determined by Western blot,and the mRNA expression level of Kcnq1ot1 was measured by reverse transcription quantitative PCR(RT-qPCR).Additionally,a rat model of myocardial is chemia reperfusion was constructed to evaluate the therapeutic potential of Suf for myocardial ischemia reperfusion injury in vivo.Results The results of bioinformatics analysis showed a direct interaction between HIF-1αand Kcnq1ot1.Compared with the Ctrl group,the H/R group showed significantly reduced H9c2 cell viability,increased cell apoptosis,and significantly upregulated concentrations of CK-MB and HBDH,along with significantly enhanced expression of HIF-1αand Kcnq1ot1(all P<0.05).When H9c2 cells were transfected with oe-HIF-1α,cell viability further decreased,apoptosis was worsened,and CK-MB and HBDH concentrations further increased(all P<0.05);however,these adverse effects were significantly inhibited when combined with Suf intervention(all P<0.05).Additionally,compared with the H/R group,the sh-HIF-1αgroup showed significantly improved cell viability,reduced apoptosis and decreased CK-MB and HBDH concentrations(all P<0.05);however,these improvements were partially reversed upon transfection with Kcnq1ot1(all P<0.05).Animal ex

关 键 词：舒芬太尼 缺氧诱导因子-Α KCNQ1重叠转录物1 心肌缺氧-复氧损伤 缺血/再灌注损伤 心肌损伤 

分 类 号：R-332[医药卫生] R329.25R329.411R542.2R845.22R971.2