丹羚心舒胶囊对大鼠离体心脏缺血/再灌注损伤的保护作用
| 作者: |
1高琦,
1黄文东,
1苏妹玲,
1杨永飞,
1曾智,
1朱邦豪
1 中山大学中山医学院心血管研究中心，广州 510080 |
| 通讯: |
高琦
Email: 375011342@qq.com |
| DOI: | 10.3978/j.issn.2095-6959.2014.06.019 |
摘要
目的：研究丹羚心舒胶囊(Danlingxinshu capsule，DLXSS)对大鼠离体心脏缺血/再灌注(myocardial ischemia/reperfusion，I/R)损伤的作用及其作用机制。方法：SD大鼠35只，随机分为5组(n=7)， 分别是空白对照组(normal)、模型组(I/R)、DLXSS高(I/R+H)、中(I/R+M)、低剂量组(9I/R+L) (96，32，11 mg/kg)。DLXSS给药组大鼠每天灌胃给药1次，连续给药7 d，空白对照组和模型组 同时给予同体积生理盐水。末次给药60 min后，分离心脏置于Langendorff离体灌流装置上，平衡 灌注20 min后，全心停灌20 min，再灌注60 min；正常对照组连续灌流100 min。于大鼠左心房插 入水囊导管，采用labchart生物信号采集仪器记录观察各受试药物组左心室收缩压(left ventricular systolic pressure，LVSP)、左心室发展压(left ventricular developed pressure，LVDP)、心率(heart rate，HR)、左心室内压最大上升速率(+dp/dtMax)、左心室内压最大下降速率(–dp/dtMax)等心动力 学指标的影响，同时在相应的时间点分别测定冠脉流出液中的乳酸脱氢酶(lactate dehydrogenase， LDH)、肌酸激酶(creatine kinase，CK)、SOD、MDA活性。HE观察组织形态学改变。结果：与模 型组相比较，DLXSS不同剂量组可明显改善缺血/再灌注所致的大鼠的心功能损伤，LVDP、±dp/ dtMax明显升高(P<0.05或者P<0.01)；冠脉流出液中LDH、CK、活性明显低于I/R组(P<0.05或者 P<0.01)，而SOD活性高于I/R组，MDA含量明显低于I/R组(P<0.05)。HE染色结果显示，DLXSS 高、中、低剂量组均不同程度的减轻了I/R造成的心肌损伤。结论：DLXSS对心肌缺血/再灌注损 伤具有保护作用，其机制可能与改善心肌舒缩功能，清除氧自由基有关。
关键词：
丹羚心舒胶囊
Langendorff
心脏血流动力学
心肌缺血/再灌注
Protective effects of DLXSS on ischemia/reperfusion injury in isolated rat hearts
CorrespondingAuthor: GAO Qi Email: 375011342@qq.com
DOI: 10.3978/j.issn.2095-6959.2014.06.019
Abstract
Objective: To investigate the protective effect of Danlingxinshu capsule (DLXSS) on myocardial ischemia/ reperfusion (I/R) injury in isolated rat hearts and its underlying mechanisms. Methods: Thirty-five SD rats were divided into five groups randomly (n=7): normal group; model group; DLXSS high, middle, low dose groups (96, 32, 11 mg/kg). Drug groups were gave DLXSS by intragastric administration once a day for 7 days consecutively, meanwhile the normal and model groups were administered with normal saline. A total of 60 min after last perfusion, the hearts were separated and perfused with Krebs-Henseleit (K-H) buffer solution on Langendorff apparatus. Hearts were in equilibrium for 20 min, then after 20 min of global ischemia, then were reperfused for 60 min. The normal group was perfused for 100 min consecutively. Myocardial hemodynamic parameters were monitored and recorded, such as left ventricular systolic pressure (LVSP), left ventricular developed pressure (LVDP), heart rate (HR), the maximum change rate of ventricular pressure rise and fall (±dp/dtMax). At the same time, coronary effluent was collected and biochemical parameters, such as lactate dehydrogenase (LDH), creatine kinase (CK), superoxide dismutase (SOD), malondialdehyde (MDA) in coronary effluent were measured as well. Histopathological examination of left ventricle was performed. Results: Compared with model group, administration of DLXSS significantly reduced myocardial injury and ameliorated heart function, with the increase in left ventricular systolic pressure, the maximum change rate of ventricular pressure rise and fall (±dp/ dtMax) (P<0.05 or P<0.01), and activities of LDH, CK, in effluent samples of DLXSS groups were lower than those in I/R group (P<0.05 or P<0.01), SOD activities was lower than that in I/R group, MDA content was obviously lower than the I/R group (P<0.05 or P<0.01). Histopathological examination showed that DLXSS also could ameliorate myocardial injury and heart function inordinately. Conclusion: Our results showed that DLXSS pretreatment can protect the cardiac function from the injury caused by ischemia/reperfusion, and the mechanism of pharmacological action might be related to the antioxidative activity of DLXSS.