摘要
目的通过动物实验验证利多卡因抑制中性粒细胞胞外诱捕网(NETs)减轻阿霉素引起的心脏毒性。方法将30只C57BL/6小鼠随机分为对照组、阿霉素组(DOX组)和利多卡因+阿霉素组(LIDO+DOX组),每组10只。对照组单次腹腔注射生理盐水1 mL/100 g;DOX组单次腹腔注射阿霉素15 mg/kg;LIDO+DOX组尾静脉注射利多卡因6 mg/kg,30 min后腹腔注射阿霉素15 mg/kg。于第10天,取小鼠血清检测各组小鼠磷酸肌酸激酶(CK)、磷酸肌酸激酶同工酶(CK-MB)水平;采用酶联免疫吸附试验(ELISA)检测各组小鼠血浆NETs标志物游离DNA(cf-DNA)、瓜氨酸组蛋白3(CitH3)、髓过氧化物酶-DNA(MPO-DNA)的水平;采用免疫荧光法检测各组小鼠心脏组织NETs相关标记物中CitH3、髓过氧化物酶(MPO)的表达量。结果DOX组小鼠血清CK、CK-MB水平明显高于对照组和LIDO+DOX组小鼠(P<0.05)。ELISA检测结果显示,DOX组与LIDO+DOX组小鼠血浆MPO-DNA、CitH3和cf-DNA水平明显高于对照组(P<0.05),但LIDO+DOX组小鼠血浆MPO-DNA、CitH3和cf-DNA水平明显低于DOX组(P<0.05)。免疫荧光法检测结果发现,DOX组小鼠心肌组织中MPO和CitH3表达量明显高于对照组和LIDO+DOX组(P<0.05)。结论利多卡因可能是通过抑制NETs的表达来缓解阿霉素引起的心脏毒性。
Objective To verify that lidocaine(LIDO)inhibits neutrophil extracellular traps(NETs)and alleviates doxorubicin(DOX)-induced cardiotoxicity by animal experiments.Methods A total of 30 C57BL/6 mice were randomly divided into control group,doxorubicin group(DOX group)and lidocaine+doxorubicin group(LIDO+DOX group),with 10 mice in each group.The control group was with single intraperitoneal injection of normal saline 1 mL/100 g,the DOX group was with single intraperitoneal injection of DOX 15 mg/kg,LIDO+DOX group was with tail vein injection of LIDO 6 mg/kg and intraperitoneal injection of DOX 15mg/kg after 30 min.The expression levels of serum CK and CK-MB were detected by on the 10th day.Enzyme linked immunosorbent assay(ELISA)was adopted to detect the levels of free DNA(cf-DNA),citrulline Histone 3(CitH3),myeloperoxidase-DNA(MPO-DNA).Immunofluorescence was uesed to detect the expression of CitH3 and myeloperoxidase(MPO)in NETs-related markers.Results The serum levels of CK and CK-MB in the DOX group were significantly higher than those in the control group and the LIDO+DOX group(P<0.05).The results of the ELISA assay showed that the levels of MPO-DNA,CitH3,and cf-DNA in the DOX group and the LIDO+DOX group were significantly higher than those in the control group(P<0.05),but the levels of MPO-DNA,CitH3 and cf-DNA of mice in the LIDO+DOX group were significantly lower than those in the DOX group(P<0.05).Immunofluorescence assay revealed that the expressions of MPO and CitH3 in the myocardial tissues of mice in the DOX group were significantly higher than those in the control group and the LIDO+DOX group(P<0.05).Conclusion Lidocaine may alleviate adriamycin-induced cardiotoxicity by inhibiting the expression of NETs.
作者
陈铃
孟文
朱霞
刘文涛
何学明
CHEN Ling;MENG Wen;ZHU Xia;LIU Wentao;HE Xueming(Department of Geriatrics,Lianyungang Oriental Hospital Affiliated to Bengbu Medical University,Lianyungang,Jiangsu 222042,China;Laboratory of Translational Medicine Center,Lianyungang Oriental Hospital,Lianyungang,Jiangsu 222042,China;Laboratory of Pharmacology,Nanjing Medical University,Jiangsu,Nanjing,Jiangsu 211100,China;Translational Medicine Center,Lianyungang Oriental Hospital,Lianyungang,Jiangsu 222042,China)
出处
《检验医学与临床》
CAS
2024年第9期1241-1244,1249,共5页
Laboratory Medicine and Clinic
基金
江苏省连云港市科技局重点研发计划项目(社会发展)(SF2214)
江苏省连云港市科学技术协会优选课题(Lkxyx2328)。
