| Objective1. To study the myocardial damage in rats at high altitude. We investigate the roles of oxidative stress and mitochondria, assess the effect of the drug in55m,1500m,2260m,3400m,4300m five elevation gradient.2. Evaluation the effect on myocardium in rats at high altitudes of cardiovascular system drugs intervention.3. To find the mechanism of metoprolol on the protective on rats exposed to acute high altitude myocardium oxidative stress and mitochondrial damage.Method1. The wistar rats were randomly divided into five groups (n=12), group A (Shanghai55m), group B (Lanzhou Gansu1500m), group C (Xining Qinghai2260m).group D (Luqu Gansu3400m) and group E (Maduo Qinghai4300m), respectively from the plain area (Shanghai55m) radical to these area. All experiment conducted of the rats witch exposed to hypoxia3days after radical altitude with low atmospheric pressure environment. To record the weight of rats at1day and3day, the blood pressure and heart rate of the groups of drug, the weight organ of rats, and take vein blood from the orbital venous for biochemical detection (serum CK, CK-MB, MYO, Tn-I, AST, HDBH, LDH etc). The blood gas analysis of abdominal arterial blood after anesthesia expermental animal (pH. pO2, pCO2, Hct. ctHb,cHCO3,BB. BE. sO2etc.) Take the heart of rats, cut part of the tissues were fixed for the pathological and electron microscopic observation. The remaining myocardial were cryopreservation tissue using liquid nitrogen, used for the determination of the level of oxidative stress (SOD, MDA, NO).2. The drugs for cardiovascular system:Amiodarone, Captopril, metoprolol, furosemide and dexamethasone were given to the rats at3400m area. All experiment conducted of the rats witch exposed to hypoxia3days after radical altitude with low atmospheric pressure environment. Recorded the weight of rats at1day and3day, the blood pressure and heart rate of the groups of drug, the weight organ of rats, and take vein blood from the orbital venous for biochemical detection (serum CK, CK-MB, MYO, Tn-I, AST, HDBH, LDH etc). The blood gas analysis of abdominal arterial blood after anesthesia expermental animal (pH, pO2, pCO2, Hct, ctHb, cHCO3, BB, BE, sO2etc.) Take the heart of rats, cut part of the tissues were fixed for the pathological and electron microscopic observation. The remaining myocardial were cryopreservation tissue using liquid nitrogen, used for the determination of the level of oxidative stress (SOD, MDA, NO).3. Determination the mitochondrial and ATP contents of model group and metoprolo groups at3400m.Results1. Compared with group A, the results of myocardial enzyme spectrum analysis of rats in group C, D and E were more increased (P<0.05). CK, CK-MB at the group B increased43.87%,55.36%; and the group C increased185.14%,84.54%; the group D increased73.54%,139.46%; and the group E increased118.28%,175.32%, therefore the enzyme of myocardial were increased significantly at blood (P<0.05). The rats myocardial markers (MYO,Tn-I):the group C. D and E were increased (P<0.05), group B increased15.36%,6.10%, group C increased182.82%,21.30%, group D increased328.35%,54.73%, group E increased444.04%,62.67%(P<0.05). With the increase in elevation the arterial partial pressure of oxygen and carbon dioxide partial pressure were significantly decreased (P<0.05); SOD and NO were decreased with increasing altitude, the group B,C,D and E were decreased10.06%,13.51%.12.18%,29.92%(P<0.05), MDA increased significantly,the group B, C, D, E were increased14.67%,89.33%,36.01%,86.66%(P<0.05), NO decreased significantly, the group B,C,D and E were decreased64.45%,65.49%,66.94%,40.54%(P<0.05). Therefore the damage of oxidative stress were increased significantly at the high altitude (≥2260m) in the fist experiment2. There were obviously improve myocardial enzymes increased, decreased the levels of MDA (25.49%, P<0.05), increased NO and SOD levels (10.75%,144.65%, P<0.05) atrer application of metoprolol, and the oxygen partial pressure and partial pressure of carbon dioxide were increased dignificantly(31.68%, P<0.05) in the second experiment.3. The content of mitochondrial complex Ⅰ,Ⅱ,Ⅲand Ⅳ in the plateau model were decreased compared with the plain group, and the contents of COM-Ⅰ, COM-Ⅲ were decreased significantly,(decreased26.17%,24.21%,17.94%,32.61%P<0.05), the vitality were enhanced after application of metoprolol (withc increased22.48%,44.01%,36.01%,17.23%(P<0.05),the same ATP content increased significantly after application of drugs (P<0.05) at3400m. 4. Myocardial histopathology and electron microscope results showed that altitude group (≥2260m) were more damaged than plain group significantly(P<0.05). and there was different degrees of improvement after the drug was administered, the group of metoprolol was significantly (P<0.05)Conclusion1. Myocardial enzymes and Tn-I. MYO released from the tissues of heart to the blood were increased with the increased of elevation during expoused to altitude of2260m.3400m.4300m, in which CK, CK-MB. Tn-I, MYO were more significantly. And the oxidative stress results also show that the negative effect brought by oxygen radical under the plateau environment, indicate the myocardial damage under the acute hypoxia, they instruction the myocardial damage were significantly at the altitude (≥2260m). There could be the compensatory respiratory alkalosis and metabolic acidosis in the rats of the elevation of2260m.3400m,4300m under the high altitude, which caused by the arterial partial pressure of oxygen, carbon dioxide partial pressure were decreased, and BE and HCO3were increased, witch the increase of elevation has aggravated the trend.2. the cardiovascular drug shave different roles in resistance to oxidative stress and biochemical, among them metoprolol against oxidative damage and improve the sO2has good effect.3. The contents of mitochondria and respiratory chain were decreased at exposed3400m, which be the cause of the ROS produced that mitochondrial complex Ⅰ, Ⅱ and Ⅲwere the main place. Application of metoprolol could obviously improve the mitochondrial damage in acute high altitude, and myocardial tissue in platau environment the oxidative damage and mitochondrial had significant negative correlation. |
PDF Full Text Request