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AIM To investigate the effect of citric acid and L-malate, two main components of Fructus Chwerospondiatis, on myocardial ischemia-reperfusion (I-R) injury and the underlying mechanisms.METHODS Rats were pretreated with citric acid and L-malate (0.5 and 0.25 g·kg-1) in 3 consecutive days, respectively.At lh after the last administration, rats were subjected to 40 min ischemia by occluding the left anterior descending coronary artery and 120 rain reperfusion.Myocardial infarct size, serum levels of tumor necrosis factor-or (TNF-α) and interleukin-6 (IL-6), the maximum platelet aggregation rate were assessed.Furthermore, the direct effects of citric acid and L-malate against cardiomyocyte necrosis and apoptosis were investigated in in vitro experiments.In the presence of citric acid, L-malate (200, 100 and 50 mg·L-1) and dihizem(45 rag·L-1), a positive control, neonatal rat cardiomyocytes were subjected to 3 h hypoxia followed by 2 h reoxygenation for necrosis (valued with the release of LDH in the culture medium)or 6 h reoxygenation for apoptosis studies (valued with flow cytometry).RESULTS We found that pretreatment with citric acid and L-malate (0.5 and 0.25 g· kg-1) significantly reduced myocardial infarct size, the maximum platelet aggregation rate and the serum level of TNF-α (P < 0.05 or P < 0.01), but not significantly reduced that of IL-6.In vitro experiments revealed that after 3 h hypoxia followed by 2 h reoxygenation (H-R) injury, the LDH levels were markedly increased in the medium of cardiomyocytes.In contrast,citric acid and L-malate (200 mg· L-1) treatment significandy reduced LDH release compared with the HR group (P < 0.05 or P <0.01).The apoptosis rate of HR-induced cardiomyocytes significantly increased, whereas treatment with citric acid and L-malate (400and 200 mg· L-1) significantly reduced the rate of apoptosis in cells (P < 0.05 or P < 0.01).CONCLUSION Our results demonstrate citric acid and L-malate play a pivotal role in the protection on myocardial I-R injury, which is possible due to their anti-inflammation and anti-platelet aggregation effects and direct protective effects on cardiomyocytes and suggest that we should attach great importance to organic acids in Chinese herbs and its application in cardiovascular diseases.