天津医药

天津医药 ›› 2015, Vol. 43 ›› Issue (5): 491-495.doi: 10.11958/j.issn.0253-9896.2015.05.012

• 专题研究-缺血与再灌注损伤 • 上一篇    下一篇

地奥心血康对大鼠心肌缺血再灌注损伤的治疗作用

郑海娟 1,2， 王维亭 2， 郝春华 2， 赵专友 2， 汤立达 2△#br#   

  1. 1天津医科大学基础医学院 （邮编 300070）； 2天津药物研究院新药评价有限公司
  • 收稿日期:2014-09-10 修回日期:2015-01-09 出版日期:2015-05-15 发布日期:2015-05-25
  • 通讯作者: 汤立达 E-mail： tangld@tjipr.com E-mail:tangld@tjipr.com
  • 作者简介:郑海娟 （1988）， 女， 硕士研究生， 主要从事心血管药理学研究

Therapeutic effects of Di’ ao Xinxuekang on myocardial ischemia-reperfusion injury in rats

ZHENG Haijuan1,2, WANG Weiting2, HAO Chunhua, ZHAO Zhuanyou2, TANG Lida2△#br# #br#   

  1. 1 Tianjin Medical University, Basic Medical College, Tianjin 300070, China; 2 Tianjin Institution for New Drug Assessment Ltd
  • Received:2014-09-10 Revised:2015-01-09 Published:2015-05-15 Online:2015-05-25
  • Contact: TANG Lida,E-mail： tangld@tjipr.com E-mail:tangld@tjipr.com

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摘要： 摘要： 目的 观察地奥心血康（DAXXK）对大鼠心肌缺血再灌注损伤的治疗作用及机制。方法 40 只 SD 大鼠经结扎冠脉左前降支制备大鼠心肌缺血再灌注损伤模型， 造模成功后随机分为模型组、 DAXXK-d（31.5 mg/kg）组、 DAXXK–g （63.0 mg/kg） 组、 合心爽 （24.8 mg/kg） 组及假手术组， 各组采用相应治疗给药， 每天 1 次， 连续 7 d。彩色多普勒超声仪测定心脏功能与心脏构型， Millar 导管法测定血流动力学， i-STAT 300 型血气分析仪测动脉血氧饱和度、血氧分压， ELISA 法测定炎性因子白细胞介素 （IL） -1β、 IL-6、 肿瘤坏死因子 （TNF） –α、 细胞间黏附分子 （ICAM） –1、血管内皮细胞黏附分子（VCAM） -1， 以及凋亡相关蛋白 Bcl-2、 Bax， TUNEL 法测定心肌细胞凋亡情况。结果 与模型组相比， DAXXK 可以增加左室缩短分数（FS）， 改善心脏收缩功能和舒张功能， 增加左室内压最大上升/下降速率（±LVdp/dtmax）。DAXXK 可减轻肺淤血导致的肺泡气体交换障碍， 增加动脉血氧分压与血氧含量， 改善肺功能， 降低 IL-1β、 IL-6、 TNF-α炎症因子水平以及 ICAM-1、 VCAM-1 水平。DAXXK 可使心肌细胞肿胀和炎性细胞浸润减轻、心肌细胞调亡减少、 Bcl-2 蛋白表达升高、 Bax 蛋白表达降低。结论 用 DAXXK 治疗对心肌缺血再灌注损伤有明显的保护作用， 其机制与抑制细胞凋亡， 减轻炎性因子损伤有关。

关键词: 心肌再灌注损伤, 心脏功能试验, 细胞黏附分子, 细胞凋亡, 炎症因子, 地奥心血康

Abstract: Abstract:Objective To observe the therapeutic effect of Di’ ao Xinxuekang (DAXXK) on myocardial ischemia-reper⁃ fusion injury in rats, and to explore its mechanisms. Methods The myocardial ischemia-reperfusion injury model was es⁃ tablished by the ligation of descending coronary artery in rats. Then animals after the modeling were randomized into model group, DAXXK-d (31.5 mg/kg) group, DAXXK-g (63.0 mg/kg) group and Diltiazem (24.8 mg/kg) group. A separate sham group was used as control. The treatment group was given DAXXK once a day for 7 days. Cardiac function and cardiac config⁃ uration were measured by color Doppler ultrasound diagnostic method. Hemodynamics was measured by Millar catheter method. The arterial oxygen saturation and blood oxygen pressure were measured by i-STAT 300 blood gas analyzer. Inflam⁃ matory cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, adhesion molecules VCAM-1, ICAM-1, and apoptosis-related protein Bcl-2, Bax were detected by ELISA. Myocardial apoptosis was measured using TUNEL method. Results Compared with model group, the left ventricular fractional shortening (FS), the systolic and diastolic function were improved, and the left ventricular pressure maximum rise / fall rates (± LVdp/dtmax) were increased, in DAXXK group. DAXXK improved lung function, increased arterial oxygen pressure and oxygen content. The inflammatory cytokines IL-1β, IL-6, TNF-α and adhesion molecules ICAM-1 and VCAM-1 were decreased in DAXXK group. The myocardial swelling and inflammatory infiltration were relieved, myocardial apoptosis was reduced, the expression of Bcl-2 protein was increased and the expression of Bax protein was decreased in DAXXK group. Conclusion DAXXK can protect myocardial ischemiareperfusion injury, which involved in the inhibition of apoptosis and reduction of inflammatory cytokines.

Key words: Di’ao Xinxue Kang(DAXXK), myocardial ischemia-reperfusion injure, apoptosis, adhesion molecules, inflammatory cytokines