| High altitude pulmonary edema is a non-cardiogenic pulmonary edema caused by severe acute hypoxia on rapid entry into the plateau.It has the characteristics of acute onset and rapid onset,mainly occurs in high altitude areas above 3000 meters,with an incidence rate of 2%,which seriously threatens the life and health of workers at high altitude.Therefore,the study of high altitude pulmonary edema is of great significance.Hypoxic environment and strenuous exercise are the main factors leading to the onset of HPE.Salidroside is the main pharmacological component of anti-hypoxia drug rhodiola capsule,which has significant anti-hypoxia and anti-oxidation effects,but the protective effect of salidroside on high altitude pulmonary edema caused by high altitude hypoxia is not clear.Therefore,this study will explore the prevention and treatment effect of salidroside on high altitude pulmonary edema,and provide new treatment drugs for high altitude pulmonary edema.It is of great significance to improve the health level of plateau workers.This thesis will carry out relevant research through the following three parts.Part I: Protective effect of salidroside on lung tissue of rats rapidly entering high altitudeWistar rats were rushed from an altitude of 1500 m to a plateau field laboratory at an altitude of 4010 m within 12 h to establish a rat model of rapid entry to high altitude hypoxia.To explore the preventive and therapeutic effects of different concentrations of salidroside on lung tissue injury in rats undergoing rapid altitude hypoxia by detecting blood gas indexes,oxidative stress,inflammatory factors and pathological damage.The results showed that,compared with the plain group,the arterial partial pressure of oxygen,blood p H,standard bicarbonate and actual bicarbonate levels were significantly decreased,the hemoglobin level was significantly increased(all P< 0.05),and the blood oxygen saturation was significantly decreased by 9.85%(P<0.01)in the rapidly entered plateau rats.In the model control group,the content of GSH in lung tissue decreased by37.83%(P<0.01),the content of T-SOD decreased by 35.25%(P<0.01),and the content of MDA increased by 22.22%(P<0.01).The serum levels of MCP-1,IL-6 and IL-1β were significantly increased,while the level of interferon-γ was significantly decreased(all P<0.01).Compared with the hypoxia model group,the arterial oxygen saturation of the rhodiola capsule group and each dose of salidroside group increased.Compared with the hypoxia control group,the arterial oxygen saturation of the high-dose salidroside group increased by4.39%(P<0.01),the blood p H,standard bicarbonate and actual bicarbonate increased significantly,and the hemoglobin level decreased significantly.The contents of glutathione and total superoxide dismutase in lung tissue were significantly increased,and the content of malondialdehyde was significantly decreased.The levels of serum inflammatory factors MCP-1,IL-6 and IL-1β were significantly decreased,and the level of interferon-γ was significantly increased.HE staining showed that in the rats entering plateau rapidly,there were exudates and a large number of inflammatory cells and red blood cells in the alveolar cavity,some lung compartments were thickened,the bronchial epithelium was disorderly,the bronchial cavity was narrowed and deformed,and a large number of inflammatory cells were aggregated.After administration of rhodiola capsule and different doses of salidroside,the alveolar exudate and inflammatory cells in alveolar cavity decreased,the exudation of red blood cells decreased,the cell wall gradually became thinner,the alveolar wall gradually became complete,and the pathological damage of lung tissue was significantly improved.The content of Occludin protein in the hypoxia model group was significantly lower than that in the blank control group(P< 0.05),and the content of Occludin protein in the high dose salidroside group was significantly higher than that in the hypoxia model group(P<0.01).Part II: The preventive and therapeutic effects of salidroside on high altitude pulmonary edemaTo evaluate the preventive and therapeutic effects of different doses of salidroside on high altitude pulmonary edema by measuring lung water content,protein and inflammatory factor levels in BALF,tissue oxidative stress and pathological damage.The results showed that: Compared with the plain group,the lung water content of the rats in the high altitude pulmonary edema model group increased by 1.51%(P<0.01),the content of bronchoalveolar lavage protein in the lung tissue increased by 147.62%(P<0.01),and the content of inflammatory factors IL-6,IL-1β and TNF-α increased significantly(all P< 0.01).The contents of glutathione and total superoxide dismutase in lung tissue were significantly decreased,and the content of malondialdehyde was significantly increased(all P< 0.01).Compared with the high altitude pulmonary edema model group,the water content of lung tissue,the protein content of alveolar lavage fluid,inflammatory factors and oxidative stress indexes were improved to varying degrees after administration of different doses of salidroside,rhodioloside capsule and dexamethasone.The water content of lung tissue decreased significantly after administration of all doses of salidroside(all P<0.01).HE staining showed that compared with the plain control group,there was a large amount of edema fluid in the alveolar cavity of the high altitude pulmonary edema model rats,and the capillaries in the alveolar wall were dilated.After administration of salidroside,rhodiola capsule,and dexamethasone,the damage in the lung tissue was alleviated.Part Ⅲ is to explore the mechanism of salidroside in the prevention and treatment of high altitude pulmonary edema based on network pharmacology.The potential targets of salidroside in the treatment of high altitude pulmonary edema were screened based on network pharmacology.Western Blot was used to detect the changes of Akt/PI3K/m TOR pathway,and to explore the mechanism of salidroside in the prevention and treatment of high altitude pulmonary edema.Through network pharmacology analysis,the main targets of salidroside against high altitude pulmonary edema were AKT1,MMP-9,TNF,IL-6,VEGF-α and other targets.The anti-HPE effect of salidroside was mainly involved in the signaling pathways of cancer,fluid shear stress and atherosclerosis,PI3K-AKT and so on.Western Blot results showed that compared with the blank control group,the expression levels of p-AKT1,p-PI3 k and p-m TOR in the lung tissue of the high altitude pulmonary edema model group increased,and the protein expression levels decreased after administration of different doses of salidroside.Salidroside may play a role in the prevention and treatment of high altitude pulmonary edema through PI3K/AKT/m TOR signaling pathway.The following conclusions were obtained: 1.Salidroside can improve the hypoxic state,correct acidosis,inhibit inflammatory response and oxidative stress,and has protective effects on lung tissue injury caused by high altitude hypoxia in rats.2.Salidroside can alleviate the increase of lung tissue water content,protein content in alveolar lavage fluid and inflammatory factors in rats with high altitude pulmonary edema,improve lung lesions,and has the effect of prevention and treatment of high altitude pulmonary edema.3.The mechanism of salidroside in the prevention and treatment of high altitude pulmonary edema may play a role by down-regulating PI3K/AKT/m TOR signaling pathway to inhibit inflammatory factors. |
PDF Full Text Request