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[摘要]
目的研究西红花酸对大鼠心肌缺血再灌注损伤的保护作用及可能的机制。方法梗死模型,结扎大鼠左前降支冠状动脉45min,再灌注180min测定心肌梗死率,并于缺血前和再灌注5、60、180min测定血清中的肌酸激酶(CK)和乳酸脱氢酶(LDH)活性。顿抑模型,结扎大鼠左前降支冠状动脉15min,再灌注180min测定缺血和非缺血心肌组织中Na+,K+-ATP酶、Ca2+,Mg2+-ATP酶活性、总腺苷酸(TAC)的量、能荷(EC)和血清中丙二醛(MDA)的量。并于缺血前、缺血末,再灌注5、30、90、180min时测定心率、左心室内收缩压、舒张压、射血分数、最大和最小左心室内压变化速率(±dp/dt)、最大和最小左心室容积变化速率(±dV/dt)以及每搏功。结果缺血前或者再灌注前给予西红花酸能够显著降低心肌梗死率,呈剂量依赖关系;并且降低血清中CK和LDH的活性。50mg/kg西红花酸可以改善心脏功能,减轻心肌顿抑的程度,升高心肌组织ATP的量及EC。结论西红花酸可以有效抑制因心肌缺血和再灌注引发的心肌梗死,缓解心肌顿抑,西红花酸可能是通过改善心肌能量代谢发挥其抗心肌缺血再灌注损伤作用的。
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[Abstract]
Objective To study the protection of crocetin on myocardial ischemia-reperfusion injury and the possible mechanism involved. Methods Infarction model: Coronary occlusion was maintained for 45 min and reperfused for 180 min to produce infarction model. Creatine kinase (CK) and lactate dehydrogenase (LDH) activity in serum of infarction groups were analyzed at baseline (before ischemia), 5, 60, and 180 min after reperfusion. Stunned model: Stunned model was achieved by ligating the left anterior descending branch of coranary artery for 15 min. Na+, K+-ATPase, and Ca2+, Mg2+-ATPase activity, total adenosine content (TAC), and energy charge (EC) in ischemic and nonischaemic myocardial tissue and malondialdehyde (MDA) in serum of stunned groups were analyzed at the end of 180 min of reperfusion. Haemodynamic parameters including heart rate, left ventricular end-systolic and end-diastolic pressure, ejection fraction, maximum and minimum dp/dt, maximum and minimum dV/dt, and stroke work, were monitored at baseline, 5, 30, 90, and 180 min after reperfusion.Methods Crocetin could attenuate the infarction ratio, relieve stunning in a dose-dependent manner, and decrease the CK and LDH activities in serum. Crocetin (50 mg/kg) could improve the heart function, ameliorate myocardial stunning degree, and increase the level of ATP and EC in myocardial tissue. Conclusion Crocetin could protect myocardium from ischemia and following reperfusion, then prevent the myocardial infarction and relieve myocardial stunning. The underlying mechanism may be partly attributed to the improvement of energy restoration and free radical scavenging effect.
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