摘要
目的探讨建立稳定阿霉素(ADR)致大鼠慢性心力衰竭(CHF)模型的方法及规范模型评价指标。方法Wistar大鼠分3批,每批分为空白组(A、D、G),模型组(B、E、H),阳性药组(C、F、I)。试验开始后B、C组腹腔注射ADR 1.5 mg/kg,2次/w,连续9 w,A组同时腹腔注射同体积生理盐水10 ml/kg;C组灌胃芪苈强心胶囊0.33 g/kg,1次/d,连续63 d,A组、B组同时灌胃同体积蒸馏水10 ml/kg;E、F组腹腔注射ADR 2.0 mg/kg,1次/w,连续13 w,D组同时腹腔注射同体积生理盐水10 ml/kg;F组灌胃芪苈强心胶囊0.33 g/kg,1次/d,连续91 d,D、E组同时灌胃同体积蒸馏水10 ml/kg;H组、I组腹腔注射ADR 3.0 mg/kg,1次/w,连续8 w,G组同时腹腔注射同体积生理盐水10 ml/kg;I组灌胃芪苈强心胶囊0.33 g/kg,1次/d,连续56 d,G、H组同时灌胃同体积蒸馏水10 ml/kg。试验结束后观察大鼠存活率、心功能、心脏指数、心肌组织病理形态改变及心肌细胞凋亡情况,酶联免疫吸附试验(ELISA)检测心肌组织B型利钠肽(BNP)含量,Western印迹检测心肌组织Caspase3、Bcl-2、Bax蛋白表达。结果3.0 mg/kg ADR组大鼠存活率高于1.5、2.0 mg/kg ADR组。与空白组比较,模型组左心室收缩压(LVSDP)、左心室内压最大上升/下降速率(±dp/dt max)、心脏指数均显著降低(P<0.01;P<0.05),BNP含量显著升高(P<0.01);心肌出现病理损伤,左心室心肌壁厚度显著降低(P<0.01),心肌凋亡指数显著升高(P<0.01),心肌组织蛋白Caspase3、Bax表达增加(P<0.05),Bcl-2表达降低(P<0.05),心肌细胞凋亡明显(P<0.05)。芪苈强心胶囊治疗后,各项检测指标与模型组比较均有显著改善(均P<0.05)。结论采用腹腔注射ADR 3.0 mg/kg,1次/w,连续8 w的方法可制备稳定的CHF动物模型。
Objective To establish a model of chronic heart failure induced by adriamycin and to standardize the evaluation index of the model.Methods Wistar rats were divided into three groups,each group was divided into blank group(A,D,G),model group(B,E,H),and positive drug(C,F,I).After the start of the experiment,group B and group C were intraperitoneally injected with adriamycin 1.5 mg/kg twice a week for 9 consecutive weeks,while group A was intraperitoneally injected with 10 ml/kg normal saline of the same volume.Group C was given 0.33 g/kg qiliqiangxin capsule once a day for 63 consecutive days.Group A and group B were given 10 ml/kg of distilled water of the same volume;Group E and group F were intraperitoneally injected with adriamycin 2.0 mg/kg once a week for 13 weeks,while group D was intraperitoneally injected with 10 ml/kg normal saline of the same volume.Group F was given 0.33 g/kg qiliqiangxin capsule once a day for 91 consecutive days.Group D and group E were given 10 ml/kg of distilled water of the same volume.Adriamycin was intraperitoneally injected into group H and group I at 3.0 mg/kg once a week for 8 consecutive weeks.Meanwhile,10 ml/kg of normal saline of the same volume was intraperitoneally injected into group G.Group I was given 0.33 g/kg qiliqiangxin capsule once a day for 56 consecutive days.Group g and group H were given 10 ml/kg of distilled water of the same volume.After the end of the experiment,the survival rate,cardiac function,cardiac weight index,pathological changes of myocardial tissue and myocardial cell apoptosis were observed.The content of B-type natriuretic peptide(BNP)was detected by ELISA,and the protein expressions of Caspase3,Bax and Bcl-2 were detected by Western blot.Results The survival rates of rats in the 3.0 mg/kg group were higher than those in the 1.5 mg/kg and 2.0 mg/kg groups.Compared with the control group,LVSP,±dp/dt Max and cardiac weight index in the 3.0 mg/kg model group were significantly lower(P<0.01 or P<0.05),while BNP content was significantly higher(P<0.01).The myocardium was pathologically damaged.The thickness of left ventricular myocardial wall was significantly decreased(P<0.01),myocardial apoptosis index was significantly increased(P<0.01),the expressions of cardiac tissue proteins Caspase 3 and Bax were increased(P<0.05),and the expression of Bcl-2 was decreased(P<0.05),which promoted the apoptosis of myocardial cells.By positive drug qiliqiangxin capsule treatment,compared with the model group,the test indicators had been significantly improved.Conclusions Stable animal models of chronic heart failure were prepared by intraperitoneal injection of doxorubicin 3.0 mg/kg once a week for 8 weeks.The model could be evaluated objectively by detecting cardiac function,cardiac mass index,BNP content and myocardial pathological changes.
作者
张译心
纪凤兰
王鑫
王晓
刘博
温富春
丁涛
徐惠波
ZHANG Yi-Xin;JI Feng-Lan;WANG Xin(Changchun University of Traditional Chinese Medicine,Changchun 130117,Jilin,China)
出处
《中国老年学杂志》
CAS
北大核心
2021年第12期2576-2581,共6页
Chinese Journal of Gerontology
基金
国家重大新药创制专项(2018ZX09711001-009-005)。
关键词
阿霉素
慢性心力衰竭
心功能
心脏指数
Doxorubicin
Chronic heart failure
Cardiac function
Cardiac index
