The Mechanisms Of Salidroside Attenuated Acute Hypobaric Hypoxia Induced Myocardial Injury By PI3K/Akt/HIF-1? Pathway

Objcetive:sixty adult male Wistar rats were randomly divided into six groups: normal control group,salidroside group,5000 m hypobaric hypoxia group,5000 m salidroside group,8000 m hypobaric hypoxia group and 8000 m salidroside group.To study the effect of salidroside in acute hypobaric hypoxia-induced heart weight index,arterial blood gas analysis,morphological changes of heart tissue,inflammatory reaction and PI3K/AKt/HIF-1..Method: To construct the myocardial injury model,the rats were intragastric administration with salidroside(40mg/kg)lasted one week before subjected to 24 h exposure of hypobaric hypoxia chamber.dead of the rats,heart weight index and arterial blood gas analysis were implemented.Hematoxylin-Eosin(HE)was used for observing the morphological changes of heart tissue.The levels of tumor necrosis factor-?(TNF-?)and Interleukin-6(IL-6)were measured using ELISA kits.The expressions of hypoxia-inducible factor-1?(HIF-1?)with experiment rats were measured using Western blot and Immunohistochemical(IHC)staining.The expressions of PI3K/Akt signaling pathway-related proteins were detected by Western blot.Result: 1.The number of survivors exposed to 8000 m was decreased(dead six rats).However,salidroside pretreatment protected the survival of rats with simulated altitude of 8000m(no dead rats).Moreover,the others groups had no sacrificed rats.The HWI were no significantly statistical differences between in the rats exposed to simulated altitude groups(5000m and 8000m)and the control group(p>0.05).the blood p H values and lactate levels had no statistical differences in six experimental groups(p>0.05).However,salidroside pretreatment partly restored the levels of carbon dioxide partial pressure(p CO2),oxygen partial pressure(p O2),oxygen saturation(s O2)compared with the simulated altitudes of 5000 m group and 8000 m group(p<0.05).2.after exposure of rats to hypobaric hypoxia chamber(simulated altitudes of 5000 m and 8000m),the levels of IL-6 and TNF-? were significantly with control group(p<0.05).As expected,the levels of IL-6 and TNF-? were significantly decreased compared with simulated altitudes of 5000 m and 8000 m when rats with salidroside pretreatment(p<0.05).3.our study showed that characteristics of hypobaric hypoxia-induced myocardial injury were the infiltration of inflammatory cells,myocardial cell swelling,degeneration,karyopyknosis and those changes in the myocardial morphology were assessed by using HE staining and light microscopy.When rats were exposed to simulated altitudes as described above,part of the heart tissue exhibited pathologic features compared with the control groups.However,those morphological characteristics were improved by salidroside pretreatment.4.Compared with the normal group,the expression of p-PI3 K,p-Akt,and HIF-1?protein in the heart of rats at 5000 m and 8000 m hypoxia environment was significantly lower than that of the normal group(P <0.01)Pretreatment significantly increased the expression of p-PI3 K,p-Akt and HIF-1?(P <0.01).Conclusion: 1.5000 m hypobaric hypoxia group and 8000 m hypobaric hypoxia group can significantly increase the heart weight index of rats,salidroside pretreatment can significantly improve the heart weight index of rats.2.The characteristics of hypobaric hypoxia-induced myocardial injury were the infiltration of inflammatory cells,myocardial cell swelling,degeneration and karyopyknosis,however,those morphological characteristics were improved by salidroside pretreatment.3.Salidroside pretreatment can restore p CO2,p O2,s O2 level.4.Salidroside preconditioning can up-regulate the expression of p-PI3 K,p-Akt and HIF-1?protein in the rat heart tissue and regulate the inflammatory response.