Study On The Interactive Effects And The Related Mechanism Of High Temperature Heat Wave And Ozone On Coronary Heart Disease

Objectives1.The purpose of this study is to quantitatively analyze the exposure-response relationship of ozone?O₃?on daily emergency amount of coronary heart disease?CHD?in Shijiazhuang through epidemiological studies.2.The purpose of this study is also to explore the interactive effects and the mechanism of high temperature heat wave and ozone on CHD through experimental studies.Methods1.Epidemiological studiesOzone data,meteorological monitoring data were collected from June 1st to August 31st,2013 to 2017 in Shijiazhuang city.The emergency cases of CHD were collected from the four hospitals in Shijiazhuang city during the same period.Spearman's rank correlation coefficient was used for analyzing of the association between ozone,meteorological factors and other ambient pollutants in Shijiazhuang.The Empower Stats statistical software was used to assess the association of ozone and daily emergency amount of CHD,and to determine the interactive effects of ozone and other factors on emergency with CHD,based on ozone as a main exposure factor.Besides,generalized additive model was established and used for an estimation that ozone effected on CHD emergency admissions during high temperature heat waves.2.Experimental studies?1?Healthy specific-pathogen-free male ApoE^-/-mice were chosen and fed with the high-fat diet to develop the atherosclerotic?AS?mice model.The weather processes of an actual heat wave and different degrees of ozone pollution were simulated in the Shanghai Meteorological and Environmental Animal Exposure System?Shanghai-METAS?.Then,a total of 64 ApoE^-/-mice,matched by weight,were randomly divided into 8 groups.Ozone-alone exposure and heat wave groups mice were randomly placed into the control cabin when the exposure system is stable,simultaneously,the heat wave plus ozone groups?mild,medium and severe?were placed in the exposure cabin,which were exposed to heat wave and different levels of ozone.Experimental mice were removed,and the physiological function indexes were measured after the exposure completed,then,the mice were sacrificed through decollation and related biological specimens were collected.?2?Biomarker estimations:Pathological sections were taken from the myocardial tissue,and related tissue markers were detected by assay kits.The concentrations of D-lactate dehydrogenase?D-LDH?,heat shock protein-60?HSP60?,tumor necrosis factor alpha?TNF-??,interleukin-6?IL-6?,intercellular adhesion molecule 1?sICAM-1?,hypoxia inducible factor 1 alpha?HIF-1??,Interferon-??IFN-??,endothelin-1?ET-1?,D-dimer?D2D?,plasminogen activator inhibitor-1?PAI-1?and malondialdehyde?MDA?were determined by using ELISA kits and a microplate reader.The activities of creatine kinase?CK?nitric oxide?NO?and superoxide dismutase?SOD?were detected by colorimetric,microplate and WST-1method,respectively.The levels of four lipids?T-CHO,TG,LDL-C,HDL-C?were determined by biochemical kit methods.Results1.Epidemiological studies?1?The hourly ozone concentration was characterized by a typical single-peak distribution in Shijiazhuang city.The correlation about average ozone concentration with wind speed,SO₂,CO,NO₂ and PM₁₀0 were significantly positive correlation?P<0.05?,but were negatively correlated with average pressure,relative humidity and PM_2.5.The concentration of ozone simultaneously increased with the rising altitude.?2?Daily emergency amount of CHD emerged a tendency that decreased first and then increased from 2013 to 2017 in Shijiazhuang city,which was similar to ozone change trend.In 2016 and 2017 reached a minimum and peak values,respectively.?3?There was an obviously positive correlation between the amount of daily emergency for CHD and daily mean temperature,daily maximum temperature,ozone and NO₂ concentration?P<0.05?,and negatively correlated to daily average pressure?P<0.05?,however,temperature and O₃ had the greatest influence on the amount of emergency CHD.?4?A dose-response relationship was found that between ozone and the amount of daily emergency for CHD in Shijiazhuang.When the level of ozone was more than102?g/m³,the amount of daily visits increased with the increase of ozone concentrations,relative risk?RR?was 1.052?95%CI:1.040,1.066?,but the influence was negative when ozone level was less 102?g/m³.?5?The females,the people older than 65 years were affected more sensitively on ozone.?6?The significant increase was found in the amount of emergency CHD due to ozone.During the high-temperature heat wave weather,NO_2,daily maximum temperature and ozone were obviously interactive effect on CHD.When ozone was increased by 10?g/m³,the risk of CHD was increased from 0.059%,0.123%to0.184%and 0.440%,respectively.2.Experimental studies?1?We found that heat wave combined with ozone exposure could retard the growth of body weight,increase rectal temperature and significantly decrease heart rate and blood pressure of AS mice.?2?Compared with the control group,the levels of remaining indicators increased with the alone-ozone exposure,but the activity of SOD decreased.However,a cardiac damage was most significant under heat wave combined with severe ozone exposure,and the heart function was reduced.Moreover,the levels of CK,D-LDH,NO,PAI-1,sICAM-1 and TNF-?in plasma increased significantly?P<0.05?,and the contents of HSP60,HIF-1?,CRP and MDA in hearts increased considerably?P<0.05?,but the activity of SOD decreased significantly.In addition,the levels of four blood lipid items remarkably increased?except the level of HDL-C which decreased significantly?with the ozone exposure.Conclusions1.Our findings suggest that there is a dose-response relationship between ozone concentration and the daily emergency amount of CHD in Shijiazhuang city.Beside,the highest temperature and NO₂ are interacted to ozone during the heat wave,which can significantly increase the risk of admissions for CHD.2.Combined exposure to heat wave and ozone can adversely affect the heart function.Moreover,heat wave may enhance the toxic effect of ozone exposure,thereby aggravating cardiovascular disease,especially under severe ozone exposure.3.The interactive toxic mechanism for heat wave plus ozone can be realized by provoking serious heart inflammation,reducing heart antioxidant capacity,destroying vascular endothelium function and accelerating dyslipidemia and thrombosis.