| Cardiovascular disease is common in human. The rate of the deaths caused by cardiovascular disease has been reached about40%. It has become the main reason for human death. With the increasing incidence of myocardial infarction, coronary angioplasty, bypass surgery, thrombolysis, the circulation of the cardiac surgery, organ transplantation technology to establish and carry out. After recoverying blood flow of myocardial, due to ischemia, myocardial dysfunction, energy metabolism dysfunction of cardiomyocyte, and Cardiac insufficiency further exacerbated. In clinic, hypotension, arrhythmias, heartfailure and myocardial infarction. The threat of myocardial ischemia-reperfusion injury to human health cannot be ignored. So, it is very important to research and develop the high biological activity, low toxicity and cardioprotective effect to myocardial ischemia-reperfusion injury.The mechanism of myocardial ischemia-reperfusion is very complicated, the potential mechanism may be related to the following reasons:①Oxidative stress: membrane oxidative damage, protease inactivation;②Inflammatory:ischemia and hypoxia lead to increased expression of inflammatory cytokines appear neutral granulocyte adhesion, chemotaxis, causing the microvascular contraction blockage, the cause cardiomyocyte apoptosis;③The intracellular Ca2+overload:intracellular calcium ion concentration is too high to lead cell function and structural damage;④Ventricular remodeling;⑤Mitochondrial damage:causes energy metabolism, electrolyte imbalance within the organization. Therefore, the several potential mechanisms from above may be provided for research and development of drugs against myocardial ischemia-reperfusion injury. Caffeic acid phenethyl ester (CAPE), is one of the main active ingredient in propolis with o-phenolic hydroxyl structure, it is also the flavonoids analogue. It has the wide range of biological activity, such as:anti-inflammatory, antioxidant, immunomodulatory, anti-ischemic reperfusion injury, free radical scavenging and anti-tumor.Our group through modified the structural of the CAPE structure,and screen the more bioactive CAPE derivatives:p-Nitro Caffeic acid phenethyl ester (CAPE-NO2) and p-hydroxyl coffee acid phenethyl ester (CAPE-OH).In this study, we use the SD rats as the research object and we established cardiac ischemia reperfusion model in vivo for rats, the hearts of rats was exposed through a left thoracotomy in the fourth intercostal space, and the left anterior descending artery was ligated proximally with a7-0silk sutur. Intravenous injection by caffeic acid ethyl benzene derivatives to intervene, and then observe the changes of the heart rate in rats. Measure the activity of LDH, AST and CK.Through the homogenate of myocardial tissue, we detected the MDA content and the activity of MPO. By TTC staining, we observed the myocardial infarction area of the myocardium, we detected ICAM1expression in myocardial by immunohistochemical testing.The experimental results show that:The Control groupinfarct size (35.6±5.4%) compared with the SHAM group was increased significantly (p<0.05); CAPE and derivatives group compared with the Control group, CAPE, CAPE-NO2, CAPE-OH three groups of infarct area was reduced and a significant difference (p<0.05); CAPE-OH, CAPE-NO2two groups compared with the CAPE group, CAPE-NO2group infarct area significantly with the decline, have substantially with significant (p <0.05).MPO content of myocardial tissue:The expression of MDA to SHAM group (1.1±0.19) compared to the Control group (4.2±0.26nmol/mg), MDA content increased significantly; compared with the Control group, CAPE, CAPE-NO2, CAPE-OH three groups of MDA content is reduced and there is a significant difference (p<0.05), the derivatives group compared with the CAPE group compared to only the CAPE-NO2group was statistically significantly (p<0.05) lower MDA content compared with the SHAM group CAPE-NO2MDA content remains high.The levels of cardiac enzymes:compared with the SHAM group, the control group the expression of cardiac specific indicators are significantly increased, there is a significant difference (p<0.05); CAPE CAPE-NO2the CAPE-OH three group than in the control group compared showed a significantly decreasing trend, including the decline in the extent of the CAPE-NO2group is the most obvious, but still very high compared with SHAM.Myocardial tissue of ICAM-1expression:Compared with the SHAM group, the control group, expression of ICAM-1’s expression enhanced, with a significant difference (p-<0.05), CAPE, CAPE-NO2, CAPE-OH three groups than the control group phase ICAM-1expression was significantly lower CAPE-NO2group is the most obvious, but compared with SHAM significantly enhanced the expression of ICAM-1, there is a significant difference (p<0.05).Our results confirmed that intravenous injection of CAPE-NO2significantly decreased the expression of ICAM-1, indicating its interior anti-inflammatory mechanism. |
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