刺五加注射液改善阿霉素诱导大鼠心脏收缩功能下降的作用研究  

Effect of Ciwujia Injection on decrease of cardiac contractile function induced by doxorubicin hydrochloride

作　　者：张珊[1] 郝春华 葛一蒙 韩冰 张蕊 王维亭 赵专友 汤立达 ZHANG Shan;HAO Chun-hua;GE Yi-meng;HAN Bing;ZHANG Rui;WANG Wei-ting;ZHAO Zhuan-you;TANG Li-da(Tianjin Medical University,Tianjin 300000,China;Tianjin Institute of Pharmaceutical Research Co.,Ltd.,Tianjin 300193,China;Harbin ZB Pharmaceutical Co.,Ltd.,Harbin 158400,China)

机构地区：[1]天津医科大学,天津300000 [2]天津药物研究院有限公司,天津300193 [3]哈尔滨珍宝制药有限公司,黑龙江哈尔滨158400

出　　处：《中草药》2018年第17期4071-4077,共7页Chinese Traditional and Herbal Drugs

摘　　要：目的研究刺五加注射液对化疗药物阿霉素诱导心脏收缩功能下降的改善作用,为其临床应用提供实验依据。方法采用阿霉素诱导大鼠心脏毒性模型,造模方法为大鼠ip 2.5 mg/kg的盐酸阿霉素,每周注射1次,共6周,累积总药量15 mg/kg。刺五加注射液高、中、低剂量(200、100、50 mg/kg)组及阳性药参芪扶正注射液(25 m L/kg)组分别于阿霉素注射后立即尾静脉输注相应的药液,时长1 h,共6次。给药结束后测定大鼠心脏收缩功能参数包括射血分数(EF)、缩短分数(FS)、左室压最大上升速率(+LVdp/dtmax)以及心脏构型。免疫组化法测定心肌细胞凋亡率;化学法测定血清超氧化物歧化酶(SOD)活性及丙二醛(MDA)、脂质过氧化物(LPO)氧化应激因子水平,酶联免疫法测定凋亡相关蛋白表达水平;电镜下观察心肌组织的超微结构变化。结果与模型组相比,刺五加注射液50、100、200 mg/kg治疗后,可改善心脏收缩功能:使下降的EF、FS、+LVdp/dtmax均显著增加(P<0.05、0.01);刺五加注射液可改善心脏构型:使扩张的收缩期的左室内径(LVIDs)明显缩短(P<0.05、0.01);使扩张的收缩期的左室腔体积(LVVs)显著缩小(P<0.05、0.01)。刺五加注射液可显著抑制阿霉素引起的心肌细胞凋亡(P<0.01),使Bax/Bcl-2显著降低(P<0.01)。刺五加注射液100、200 mg/kg可不同程度降低LPO、MDA生成量,提高SOD活性。结论刺五加注射液能有效缓解阿霉素诱导的大鼠心脏收缩功能下降,可增强心脏收缩功能、改善心脏构型,减轻心肌组织超微结构损伤,其机制可能与减轻氧化应激损伤、抑制受损心肌细胞凋亡有关。Objective To investigate the protective effect of Ciwujia Injection（CI） on the decrease of cardiac contractile function induced by doxorubicin hydrochloride, and provide experimental basis for its clinical application. Methods The cardiotoxicity model in rats was established by ip injection of doxorubicin hydrochloride with a dose of 2.5 mg/kg every week for 6 weeks, and the total cumulative dose was 15 mg/kg. Rats were equally divided into five groups with 10 rats in each group（e.g. model group, three test groups of CI, positive group）. In addition, a normal control group of 10 rats was injected intraperitoneally with normal saline（NS） once a week for 6 weeks. Normal control and model group were given NS intravenously. The test groups were given CI and the positive group was given Shenqi Fuzheng Injection. The CI and Shenqi Fuzheng Injection were infused by tail vein for 1 h when doxorubicin hydrochloride administrated. The parameters of left ventricular systolic function including ejection fraction（EF）, shortening fraction（FS）, the maximal rate of rise of left ventricular pressure（＋LVdp/dtmax）, and heart geometric shape were measured. Cardiomyocyte apoptosis was measured with immunohistochemistry, apoptosis-related protein and oxidative stress factors such as SOD, MDA, and LPO were measured with enzyme-linked immune sorbent assay, or chemical method. The ultrastructural changes of myocardium under electron microscope were observed. Results Compared with model group, after CI treatment（50, 100, and 200 mg/kg）, the cardiac systolic function was improved; the declined EF, FS, and ＋ LVdp/dtmax increased（P〈0.05, 0.01）. The heart geometric shape was improved significantly with CI treatment, the expanded LVIDs and LVVs decreased（P〈0.05, 0.01）. CI can inhibit myocardial cell apoptosis（P〈0.01）, the myocardial apoptosis rate decreased（P〈0.01）, and the Bax/Bcl-2 decreased（P〈0.01）. In addition, CI（100 and 200 mg/kg） can decline the generation of LPO, MDA and

关 键 词：刺五加注射液 阿霉素 心脏毒性 心功能 心脏构型 氧化应激 细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]