| Backgroud:Coronary heart disease become the first killer for adult. Myocardial ischemia and acute infarction arise secondary to atherosclerosis, followed by plaque rupture and thrombosis. Current treatments aim to terminate ischemiaby re-establishing blood flow as soon as possible. However, reperfusion may cause new damage, reperfusion injury, Several mechanisms have been proposed, such as rapid entry of sodium ions and water into myocardial cells producing intracellular edema during ischemia. Rapid entry of calcium ions produces the contraction bands and mitochondrial granules. Loss of vascular integrity results in hemorrhage into the infarct. Finally, the production of reactive oxygen species (ROS) is responsible for the peroxidation of membrane lipids and disruption of membrane integrity. Further, ischemia and reperfusion may alter the myocardial redox status and therefore the ability to detoxify ROS. Also, ROS can stimulate inflammation system,active NF-κB and produce pro inflammation cytokines such as IL-2,IL-6,TNF-α,INF-y, which can contribute to the server reperfusion damage.The drug which suppress ROS and inflammation is hopfully to prevent ischemia-reperfusion injury.OBJECTIVE:To investigate the protective effects of astilbin on heart ischemia-reperfusion (IR) injury in mice.from-3 levels:in vitro myocardial cell culture,ex vivo langendorff heart perfusion,in vivo LAD ligation in mice.METHODS:C57BL/6 mice were randomly allocated into 4 groups:no ischemia control group, C; Ischemia reperfusion group, I; Low dosage Astilbin treatment group,L; High dosage Astilbin treatment group, H。After ischemia reperfusion, the myocardial cells or heart from each group were studied. histological changes of the cardiac tissues were detected to evaluate injury. the level of ROS,MDA,SOD of the sample were measured by kit, TNF-a measured by RT-PCR and immunohistochemistry,NF-κB measured by EMSA.serum IL-6 level measued by ELISA, cardiac myocyte apoptosis tested by TUNELRESULTS:Compared with the untreated ischemia group, activities of SOD were diminished and ROS,MDA level increased obviously in IR group, whereas pretreatment with Astilbin significantly blunted the decrease of SOD activity, less ROS production and lower MDA level. and similar results were also found in histological examination. The NF-κB activity,expression of TNF-a mRNA and protein of cardial tissues in the astilbin group were lower than those in the untreated ischemia reperfusion group. The serum contents of IL-6 were decreased in the astilbin group as compared with the untreated ischemia reperfusion group (P<0.01).CONCLUSION:It has been well known that oxidative stress and inflammation are two major mechanismsinvolved in the development of CAD ischemia reperfusion injury, Oxidative stress is represented as increased activity of oxidant enzymes and/or reduced activity of antioxidant enzymes. ROS produced by oxidant enzymes participates in the progression of myocardial ischemia reperfusion damage in two ways:one is the direct oxidation to the membrane,mitochondria,enzyme of cardiac myocytes; the other is as an intracellular second messenger to induce expression of pro inflammation cytokines(IL-6,TNF-α), which lead to Caspase cascade and cardiac myocytes apoptosis. Astilbin can ameliorate cardiac myocytes ischemia reperfusion injury by 2 ways:1 eliminate ROS,MDA and recover SOD, rebalance the redox state; 2 inhibiting the production of pro inflammation cytokines IL-6 and TNF-a, prohibite the activity of NF-KB. Astilbin is a safe and effective medicine for anti-ischemia reperfusion injury.
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