利多卡因通过抑制NETs改善阿霉素引起的心脏毒性OACSTPCD
Lidocaine improves doxorubicin-induced cardiotoxicity by inhibiting NETs
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C57 BL/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(Cit H3)、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、Cit H3 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、Cit H3 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 C57 BL/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 in-jection 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.En-zyme linked immunosorbent assay(ELISA)was adopted to detect the levels of free DNA(cf-DNA),citrulline Histone 3(Cit H3),myeloperoxidase-DNA(MPO-DNA).Immunofluorescence was uesed to detect the expres-sion of Cit H3 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,Cit H3,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,Cit H3 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 Cit H3 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-in-duced cardiotoxicity by inhibiting the expression of NETs.
陈铃;孟文;朱霞;刘文涛;何学明
蚌埠医科大学附属连云港市东方医院老年医学科,江苏连云港 222042江苏省连云港市东方医院转化医学中心实验室,江苏连云港 222042南京医科大学药理学实验室,江苏南京 211100江苏省连云港市东方医院转化医学中心,江苏连云港 222042
临床医学
利多卡因阿霉素心脏毒性中性粒细胞胞外诱捕网
lidocainedoxorubicinNETscardiotoxicityneutrophil extracellular trap
《检验医学与临床》 2024 (009)
1241-1244,1249 / 5
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).
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