布比卡因介导apelin影响大鼠心肌细胞的基因表达  

Effect of bupivacaine mediated apelin on gene expression of rat cardiomyocytes

作　　者：陈超星 张样 林婷婷[1] 施克俭[1] 刘乐[1] Chen Chaoxing;Zhang Yang;Lin Tingting;Shi Kejian;Liu Le(Department of Anesthesiology,the First Afiliated Hospital of Wenzhou Medical University,Wenzhou 325015 China;Department of Information,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China)

机构地区：[1]温州医科大学附属第一医院麻醉科,温州325015 [2]温州医科大学附属第一医院信息科,温州325015

出　　处：《中国医师杂志》2024年第10期1470-1476,1482,共8页Journal of Chinese Physician

基　　金：国家自然科学基金(82200329,81900231)。

摘　　要：目的探讨布比卡因对SD大鼠心肌细胞apelin/APJ通路及后续基因表达的影响。方法体外培养大鼠H9C2心肌细胞,予0~1 mmol/L布比卡因处理6 h后,酶联免疫吸附试验(ELISA)检测apelin浓度,蛋白免疫印迹法(Western blot)检测APJ表达;取15只SD成年雄性大鼠随机分为假手术组(sham组)、布比卡因30 mg/kg组(Bupi组)、布比卡因30 mg/kg+[Pyr^(1)]apelin-130.15 mg/kg(Bupi-A)组,相应处理后,取心肌组织检测apelin和APJ表达,并进行高通量测序。结果Western blot和ELISA结果显示,布比卡因下调H9C2心肌细胞apelin和APJ的表达(均P<0.05)。Bupi组SD大鼠心肌组织中apelin和APJ的表达水平低于sham组(均P<0.05)。而Bupi-A组心肌组织中apelin表达水平高于Bupi组(P=0.006),但APJ表达差异无统计学意义(P>0.05)。高通量测序发现,与sham组相比,在Bupi组明显上调却在Bupi-A组明显下调的前5个差异表达基因分别是泛醌NADH脱氢酶Fe-S蛋白3、烯醇化酶1、水通道蛋白1、ATP合酶F0复合体C亚基1脂质结合蛋白、过氧化物酶2(均P<0.001);在Bupi组明显下调却在Bupi-A组明显上调的前5个基因分别为间皮素、Rho GTP酶活化蛋白29、Sten20样激酶、碳酸酐酶、旁血小板溶蛋白(均P<0.001)。这些基因与心肌细胞凋亡增加、能量代谢紊乱及运动减弱相关。结论布比卡因通过减少apelin表达,导致大鼠心肌细胞中与凋亡增加、能量代谢紊乱及运动减弱相关的基因表达改变。Objective To investigate the effect of bupivacaine on Apelin/APJ pathway and subsequent gene expression in Sprague-Dawley(SD)rat cardiomyocytes.Methods H9c2 cardiomyocytes were cultured in vitro and treated with O-1 mmol/L bupivacaine for 6 h.The concentration of Apelin was detected by enzyme-linked immunosorbent assay(ELISA),and the expression of APJ was detected by Western blot;Fifteen adult male SD rats were randomly divided into sham group(sham group),bupivacaine 30 mg/kg group(Bupi group),bupivacaine 30 mg/kg+[Pyr']apelin-130.15 mg/kg(Bupi-A)group.Afer corresponding treatment,myocardial tissue was taken to detect the expression of Apelin and APJ,and high-throughput sequencing was performed.Results Western blot and ELISA results showed that bupivacaine down regulated the expression of Apelin and APJ in H9c2 cardiomyocytes(all P<0.05).The expression levels of Apelin and APJ in the myocardial tissue of SD rats in Bupi group were lower than those in sham group(all P<0.05).The expression of Apelin in myocardial tissue of Bupi-A group was higher than that of Bupi group(P=0.006),but the expression of APJ had no significant difference(P>0.05).High throughput sequencing revealed that compared with sham group,the top five differentially expressed genes that were significantly upregulated in Bupi group but significantly downregulated in Bupi-A group were ubiquinone NADH dehydrogenase Fe-S protein 3,enolase 1,aquaporin 1,ATP synthase FO complex C subunit 1 lipid binding protein,and peroxidase 2(all P<0.001);The top five genes that were significantly down regulated in Bupi group but significantly up-regulated in Bupi-A group were mesothelin,Rho GTPase activating protein 29,sten20 like kinase,carbonic anhydrase,and paraplatelet lysin(all P<0.001).These genes were associated with increased cardiomyocyte apoptosis,energy metabolism disorders and exercise attenuation.Conclusions bupivacaine can reduce the expression of Apelin,leading to the changes of gene expression related to increased apoptosis,energy metabolism disorder

关 键 词：布比卡因 Apelin/APJ信号通路 肌细胞 心脏 

分 类 号：R614[医药卫生—麻醉学]