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脂肪乳改善布比卡因致大鼠心脏毒性机制的研究 被引量:1

Study on the mechanism of lipid emulsion on improving bupivacaine-induced cardio-toxicity in rats
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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-terminal kinase,JNK)和p38磷酸化水平明显高于空白对照组(P<0.05);给予LE处理后,ERK1/2、JNK和p38磷酸化水平明显降低(P<0.05)。结论LE可改善BPV致大鼠心脏毒性,减轻心肌应激损伤,其机制可能与调控MAPK信号通路、抑制细胞凋亡有关。 Objective 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 expression level was significantly increased(P<0.05)while the protein expression levels of Bax,cleaved caspase-3 and cleaved caspase-9 were decreased(P<0.05).The phosphorylation levels of extracellular regulated protein kinases 1/2(ERK1/2),c-Jun N-terminal kinase(JNK)and p38 in the myocardial tissues of BPV control group were significantly higher than those of blank control group(P<0.05).The phosphorylation levels of ERK1/2,JNK and p-38 were significantly reduced after LE treatment(P<0.05).Conclusion LE can ameliorate BPV-induced cardiotoxicity in rats and relieve myocardial stress injury,and its mechanism may be related to the regulation of MAPK signaling pathway and the inhibition of cell apoptosis.
作者 张淑娟 孟令群 黄翠影 韩庆波 蔡立松 李军 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)
出处 《西北药学杂志》 CAS 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)。
关键词 布比卡因 脂肪乳 应激反应 心脏毒性 MAPK信号通路 bupivacaine lipid emulsion stress response cardiotoxicity MAPK signaling pathway
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