首页|强心利水方调控鸢尾素对阿霉素诱导的乳腺癌斑马鱼心肌损伤的影响

强心利水方调控鸢尾素对阿霉素诱导的乳腺癌斑马鱼心肌损伤的影响

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目的:探讨强心利水方调控鸢尾素(Irisin)对阿霉素诱导的乳腺癌斑马鱼心肌损伤的保护作用及机制。方法:通过显微注射人乳腺癌MDA-MB-231细胞构建斑马鱼乳腺癌移植瘤模型。根据斑马鱼死亡情况筛选强心利水方对荷瘤斑马鱼耐受浓度。将荷瘤斑马鱼随机分为空白对照组、阿霉素组、右丙亚胺组、强心利水方组、参麦注射液组,每组30尾。除空白对照组,其余各组给予质量浓度30 μmol/L阿霉素干预,同时右丙亚胺组、强心利水方组、参麦注射液组给予相应药物干预。于8受精后天数(dpf)各组分别取10尾斑马鱼,统计心率,测量静脉窦-动脉球(SV-BA)间距,计算每搏输出量、心输出量;苏木素-伊红(HE)染色观察斑马鱼心脏组织病理改变;酶联免疫吸附测定(ELISA)检测斑马鱼Irisin、前体心钠肽(Pro-ANP)、N末端BNP前体脑钠肽(NT-pro BNP)、心肌肌钙蛋白T(cTnT)及超敏C反应蛋白(hs-CRP)的含量变化。结果:根据斑马鱼对强心利水方最大耐受量筛选试验,本研究选取30 mg/L质量浓度作为强心利水方组的干预浓度。与空白对照组比较,阿霉素组斑马鱼心脏功能明显减退,心脏病理学观察显示存在严重的心包水肿和心脏形态显著增大,心肌纤维排列稀疏而紊乱;Irisin水平降低(P<0。01),hs-CRP、Pro-ANP、NT-pro BNP、cTnT2水平均升高(P<0。01)。与阿霉素组比较,经右丙亚胺、强心利水方、参麦注射液干预后斑马鱼心脏功能均有所改善,Irisin水平明显升高(P<0。01),hs-CRP、Pro-ANP、NT-pro BNP、cTnT2水平均有不同程度下降(P<0。05或P<0。01)。强心利水方组改善心脏功能效果优于参麦注射液组(P<0。05或P<0。01)。结论:强心利水方对阿霉素诱导的乳腺癌斑马鱼心肌损伤具有较好的保护作用,其机制可能与促进鸢尾素分泌和减轻心肌炎症反应有关。
Effect of Qiangxin Lishui Prescription(强心利水方)on Myocardial Damage by Regulating Irisin in Adriamycin-Induced Breast Cancer Zebrafish
Objective:To study the effect of Qiangxin Lishui prescription on myocardia damage induced by adriamycin in zebrafish with breast cancer according to regulating Irisin.Methods:Human breast cancer MDA-MB-231 cells were transplanted into zebrafish yolk sac by microinjection to construct the zebrafish breast cancer transplantation model.According to the death of zebrafish,the tolerance concent ration of Qiangxin Lishui prescription to tumor-bearing zebrafish was screened.Tumor-bearing Zebrafish were randomly divided into blank control group,adriamycin group,dextropropimide group,Qiangxin Lishui prescription group and and Shenmai injection(参麦注射液)group,with 30 fish in each group.The blank control group had no drug tbtervention,and the other groups were given adriamycin with mass concentration of 30 mg/L.Dextroproimide group,Qiangxin Lishui prescription group and Shenmai injection group were given corresponding measures.On the eighth days post fertilization(dpf),10 zebrafish were selected from each group.The heart rate and SV-BA distance were separately measured.The heart stroke output and cardiac output were calculated.The pathological changes were observed by hematoxylin-eosin(HE)staining in the zebrafish heart tissues.The indicators of Irisin,pro-atrial natriuretic peptide(Pro-ANP),N-terminal pro-brain natriuretic peptide(NT-pro BNP),cardiac troponin T(cTnT)and high sensitive C reactive protein(hs-CRP)were detected by enzyme-linked immunosorbent assay(ELISA).Results:According to the screening test of zebrafish's maximum tolerance to Qiangxin Lishui prescription,30 mg/L mass concentration was selected.Compared with the blank control group,the cardiac function declined in adriamycin group and Cardiac pathology showed that there were severe pericardial edema and significant enlargement in adriamycin group,meanwhile the myocardial fibers are sparsely arranged and disordered in heart.The Irisin levels decreased significantly in adriamycin group(P<0.01),while the levels of hs-CRP,Pro-ANP,NT-pro BNP and cTnT2 increased significantly in adriamycin group(P<0.01).Compared with the adriamycin group,improvements were made in the dextropropimide,Qiangxin Lishui prescription and Shenmai injection groups.The Irisin level increased in dextropropimide,Qiangxin Lishui prescription and Shenmai injection groups(P<0.01),while the levels of hs-CRP,Pro-ANP,NT-pro BNP and cTnT2 decreased significantly in varying degrees(P<0.05 or P<0.01).The Qiangxin Lishui prescription group showed better effects in improving cardiac function than Shenmai injection group(P<0.05 or P<0.01).Conclusion:Qiangxin Lishui prescription shows a protective effect on adriamycin-induced myocardia damage in breast cancer zebrafish.The mechanism may be correlated to promoting irisin secretion and reducing myocardial inflammation.

breast cancerQiangxin Lishui prescriptionzebrafishadriamycinmyocardial damageIrisin

徐拥建、廖群标、任亚冰、王媛媛、邓梦琪、陈鉴聪、程海晏、刘强

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国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院深圳医院,广东 深圳 518116

乳腺癌 强心利水方 斑马鱼 阿霉素 心肌损伤 鸢尾素

广东省中医药局科研项目中国医学科学院肿瘤医院深圳医院院内科研课题资助2021年深圳市名中医药专家传承工作室建设项目

20221358E010222009

2024

中医药导报
湖南省中医药学会 湖南省中医管理局

中医药导报

CSTPCD
影响因子:0.952
ISSN:1672-951X
年,卷(期):2024.30(6)
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