Study On Lung Injury In Hypoxic Environment At Different Altitudes From The Perspective Of Medical Geography

More than four-fifths of Qinghai province is plateau,and the high altitude and low oxygen environment is an important geographical environmental factor causing plateau pulmonary edema.Only medical analysis of the occurrence of pulmonary edema is not conducive to the clear impact of geographical environment on the disease.However,only geographical analysis of the predisposing factors of pulmonary edema fails to clarify the pathogenesis of high altitude pulmonary edema.Therefore,it is one of the approaches to better solve high altitude pulmonary edema to analyze the pathogenesis of high altitude pulmonary edema and the influence of geographical environmental factors from the perspective of medical geography by using relevant technologies and methods of medical research,and to find effective drugs for the treatment and prevention of high altitude pulmonary edema.In order to clarify the effects of geographical environmental factors at different altitudes on lung function and their molecular mechanisms,and to accurately select effective preventive drugs according to the molecular mechanism of lung injury,this paper analyzed the correlation of geographical environmental factors in three tourist resorts(Xining,Menyuan and Maduo)with an altitude difference of 1 000 m in Qinghai Province.Male SD rats of SPF grade were selected as the research subjects.The correlation between temperature,precipitation,normalized vegetation index(NDVI),oxygen content and altitude and arterial blood oxygen partial pressure,oxygen saturation,pulmonary artery pressure and lung tissue water content of rats in three regions was analyzed.The differentially expressed genes were screened and verified by transcriptome method after different periods of hypoxia stress at 4 200 m.The expression of endoplasmic reticulum stress-related proteins,inflammatory factors and apoptosis factors in lung tissues of rats at different altitudes were detected by molecular biology.The effects of hypoxia on blood oxygen partial pressure,blood oxygen saturation,pulmonary artery pressure,lung tissue water content and apoptosis related protein expression levels of rats were studied by constructing sh-Fdft 1silenced adenovirus vector and negative control vector and pretreating rats with adenovirus vector and vitamin D3.The results showed that:(1)Oxygen concentration in the atmosphere had a strong positive correlation with temperature and normalized vegetation index(R =0.967 and 1.000,respectively),and a strong negative correlation with altitude(R =-0.994).For every 1 000 m increase in altitude,air pressure decreased by 10 Kpa and oxygen concentration decreased by about 28 g/m3.(2)In the hypoxic environment of4 200 m,the pulmonary artery pressure and oxygen saturation were significantly increased(P < 0.01),and the activities of antioxidant enzymes(GSH-Px and SOD)and malondialdehyde content in lung tissues were significantly decreased(P < 0.01).The water content of lung tissue was significantly increased(P < 0.01),and the pathological damage of lung tissue was obvious,with a large number of inflammatory factors infiltrating,and the damage was significantly aggravated with the extension of stress time.In the 3 200 m altitude environment,the physiological and morphological indexes of the rats were slightly changed by continuous hypoxia stress,and the damage was relatively minor.At 2 200 m altitude,there were no significant changes in the indices above rats(P > 0.05).(3)environment in geography,altitude and blood oxygen saturation were significantly negative correlation(P < 0.05),the elevation and lung water content and pulmonary artery pressure was significantly positive correlation(P < 0.05),while the air oxygen concentration and blood oxygen saturation was significantly positive correlation(P < 0.05),the oxygen concentration in the air and lung water content and pulmonary artery pressure significantly negative correlation(P < 0.05).(4)Transcriptome sequencing analysis showed that the differential genes were mainly enriched in immune,inflammatory and metabolic pathways in the lung tissues of hypoxic rats at 4 200 m,and the nod-like receptor and key genes in downstream related signaling pathways and the steroid hormone synthesis pathway were highly expressed(P < 0.01).CARD9,MYD88,p-p38 MAPK and p-p65 proteins in the downstream p38 MAPK/NF-?B signaling pathway of nod-like receptor,and the expression levels of ER stress regulatory proteins GRP78,PERK,IRE1,ATF6,CHOP and caspase-12 in hypoxic-injured rat lung tissues were significantly increased(P < 0.05 or P < 0.01).Apoptosis rate and Cleaved caspase-3protein expression were significantly increased(P < 0.05 or P < 0.01)in rats with hypoxic injury.(5)After Fdft 1 silencing,hypoxia stress significantly decreased blood oxygen partial pressure and blood oxygen saturation(P < 0.01),significantly increased pulmonary artery pressure and lung tissue water content(P < 0.01),and significantly decreased the expression of Bcl-2 protein in lung tissue(P < 0.01).The expression levels of PCNA,Bax and Cleaved caspase-3 were significantly increased(P < 0.01).(6)Vitamin D3 significantly increased blood oxygen partial pressure and saturation in hypoxic stress group and Fdft 1 silencing group,and significantly inhibited the increase of pulmonary artery pressure and lung tissue water content,as well as the expression levels of PCNA and apoptosis-related proteins in lung(P <0.01).The above results suggest that the oxygen concentration in the atmosphere is positively correlated with normalized vegetation index and temperature,but negatively correlated with altitude,and altitude is the most important factor affecting atmospheric oxygen concentration.With the elevation of 4 200 m,pulmonary hypertension and high altitude pulmonary edema can occur in rats.Among geographical factors,altitude is the main factor affecting lung function.The p38MAPK/NF-?B pathway and endoplasmic reticulum stress mediated apoptosis and inflammatory response in rat lung tissue at high altitude contribute to pulmonary edema.Silencing a key gene(Fdft 1)involved in vitamin D3 synthesis exacerbates hypoxic pulmonary hypertension and high altitude pulmonary edema in rats.Exogenous vitamin D3 supplementation has significant preventive and protective effects on the occurrence and development of hypoxic lung injury.