脂肪乳改善布比卡因致大鼠心脏毒性机制的研究  

Study on the mechanism of lipid emulsion on improving bupivacaine-induced cardio-toxicity in rats

作　　者：张淑娟 孟令群 黄翠影 韩庆波[1] 蔡立松[1] 李军[1] ZHANG Shujuan;MENG Lingqun;HUANG Cuiying;HAN Qingbo;CAI Lisong;LI Jun(Department of Operation and Anaesthesia,Kailuan General Hospital,Tangshan 063000,China;Department of Pediatric Internal Medicine,Tangshan Maternal and Child Health Care Hospital,Tangshan 063000,China)

机构地区：[1]唐山市开滦总医院手麻科,唐山063000 [2]唐山市妇幼保健院儿内科,唐山063000

出　　处：《西北药学杂志》2022年第3期77-83,共7页Northwest Pharmaceutical Journal

基　　金：河北省2021年度医学科学研究课题计划项目(编号:20210041)。

摘　　要：目的探究脂肪乳(lipid emulsion,LE)改善布比卡因(bupivacaine,BPV)致大鼠心脏毒性的机制。方法将30只成年雄性SD大鼠随机均分为3组,分别是空白对照组、布比卡因对照组和布比卡因+脂肪乳组。检测各组大鼠心电图、血清心肌酶相关指标及应激指标,用Western blot检测心肌组织凋亡相关蛋白及丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路相关蛋白的表达。结果与空白对照组比较,布比卡因对照组大鼠心电图明显异常,表现为ST段改变;给予LE处理后,大鼠心电图异常明显改善。布比卡因对照组大鼠血清肌酸激酶同工酶MB(creatine kinase MB,CK-MB)、心肌肌钙蛋白T(cardiac troponin-T,cTn-T)、乳酸脱氢酶(lactate dehydrogenase,LDH)和脑钠肽(brain natriuretic peptide,BNP)水平明显高于空白对照组(P<0.05);布比卡因+脂肪乳组大鼠血清CK-MB、cTn-T、LDH和BNP水平明显低于布比卡因对照组(P<0.05)。布比卡因对照组大鼠血清超氧化物歧化酶(superoxide dismutase,SOD)活性、谷胱甘肽(glutathione,GSH)水平明显低于空白对照组(P<0.05),丙二醛(malondialdehyde,MDA)、NADPH氧化酶-2(NADPH oxidase 2,NOX-2)和一氧化氮水平明显高于空白对照组(P<0.05);布比卡因+脂肪乳组大鼠血清SOD活性、GSH水平明显高于布比卡因对照组(P<0.05),MDA、NOX-2和一氧化氮水平明显低于布比卡因对照组(P<0.05)。布比卡因对照组大鼠心肌组织B淋巴细胞瘤-2(B cell lymphoma-2,Bcl2)蛋白的表达水平明显低于空白对照组(P<0.05),Bcl2相关X蛋白(Bcl2 associated X protein,Bax)、cleaved caspase-3和cleaved caspase-9蛋白的表达水平明显高于空白对照组(P<0.05);给予LE处理后,Bcl2蛋白的表达水平明显升高(P<0.05),Bax、cleaved caspase-3和cleaved caspase-9蛋白的表达水平降低(P<0.05)。布比卡因对照组大鼠心肌组织细胞外调节蛋白激酶1/2(extracellular regulated protein kinases 1/2,ERK1/2)、c-Jun氨基末端激酶(c-Jun N-teObjective To explore the mechanism of lipid emulsion(LE)on improving bupivacaine(BPV)-induced cardiotoxicity in rats.Methods 30 adult male SD rats were randomly and evenly divided into 3 groups,including blank control group,BPV control group and BPV+LE group.The electrocardiogram,serum myocardial enzyme-related indicators and stress indicators of rats were detected in each group.Western blot was used to detect the expressions of apoptosis-related proteins and mitogen-activated protein kinase(MAPK)signaling pathway related proteins in myocardial tissues.Results Compared with blank control group,the electrocardiogram of rats in BPV control group was obviously abnormal,manifested as ST-segment changes.After LE treatment,the abnormal electrocardiogram of rats was significantly improved.The levels of serum creatine kinase MB(CK-MB),cardiac troponin-T(cTn-T),lactate dehydrogenase(LDH)and brain natriuretic peptide(BNP)in BPV control group were significantly higher than those in blank control group(P<0.05).The levels of serum CK-MB,cTn-T,LDH and BNP of rats in BPV+LE group were significantly lower than those in BPV control group(P<0.05).Serum superoxide dismutase(SOD)activity and glutathione(GSH)level of BPV control group were significantly lower than those of blank control group(P<0.05),while the levels of malondialdehyde(MDA),NADPH oxidase 2(NOX-2)and nitric oxide were significantly higher than those of blank control group(P<0.05).Serum SOD activity and GSH level in BPV+LE group were significantly higher than those in BPV control group(P<0.05),while the levels of MDA,NOX-2 and nitric oxide were significantly lower than those in BPV control group(P<0.05).The expression level of B cell lymphoma-2(Bcl2)protein in myocardial tissues of BPV control group was significantly lower than that of blank control group(P<0.05),while the protein expression levels of Bcl2 associated X protein(Bax),cleaved caspase-3 and cleaved caspase-9 were significantly higher than those of blank control group(P<0.05).After LE treatment,Bcl2 protein

关 键 词：布比卡因 脂肪乳 应激反应 心脏毒性 MAPK信号通路 

分 类 号：R965[医药卫生—药理学]