| Part 1 The intervention of andrographolide on lung injury in mice induced by cigarette smokeObjective: To investigate the difference and change of lung function index Penh and TV in mice under different cigarette smoke concentration and bronchial provocation test,and the changes of corresponding indexes under the intervention of andrographolide.Methods: 40 male SPF-grade BALB/c strain mice(6-8 weeks old,body weight 20-25 g)were divided into 4 groups of control,low concentration,high concentration and andrographolide,with 10 mice in each group.Mice in the low concentration group were placed in a static poison cabinet for 2 hours between 9:00-11:00 per day,exposed to total particle cigarette smoke of 100 mg/m3.Mice in the high concentration group and andrographolide were placed in a static poison cabinet for 2 hours between 11:00-13:00 and 14:00-16:00,respectively,per day,exposed to total particle cigarette smoke of 300 mg/m3 total particles in cigarette smoke.Exposure was performed five days a week.The mice in andrographolide group were injected with 20 mg/kg andrographolide solution every week from the 5th week to the 12 th week.In the 12 th week of the experiment,whole body plethysmography was performed to determine the lung function of each mouse,and the functional indicators included Penh,TV,etc.,and the bronchial provocation test was performed.The level of cytokines IL-6 and IL-8 in alveolar lavage fluid of mice were examined,and the lung tissues were dyed with HE.Results: Before acetylcholine bronchial provocation test,Penh in low concentration group was significantly higher than that in control group.After bronchial provocation test,Penh and TV of the high concentration group were significantly higher than those of the blank control group,and Penh of the high concentration group was significantly higher than that of the low concentration group(P<0.05).The changes of Penh in the control group and the high concentration group increased with the increase of the concentration of acetylcholine,changes in Penh become more sensitive under a bronchial provocation test at high concentrations of acetylcholine.Il-6 and IL-8 in alveolar lavage fluid of mice in high concentration group were significantly increased.With the increase of cigarette dose,alveolar wall rupture,alveolar structure gradually incomplete,irregular shape.There was an improvement in the andrographolide group.Conclusion: Cigarette smoke exposure will increase Penh,TV,IL-6,IL-8 of mice.Changes in Penh become more sensitive under a bronchial provocation test at high concentrations of acetylcholine.Andrographolide can ameliorate the decreased lung function induced by cigarette smoke.Part 2 The relationship between smoking behavior and lung function in the populationObjective: To investigate the relationship between smoking behavior and lung function indicators FVC,FEV1,PEF and types of lung dysfunction in the population.Methods: In 2008,we established a study cohort based on geographical region(northern Jiangsu,central Jiangsu and southern Jiangsu)in Jiangsu Province.Using a multi-stage stratified sampling method(community – family-individual),representative ordinary participants from Jiangsu Province were selected,and a total of 7680 participants were included in the statistical analysis of the study,and 6734 people were included in the statistical analysis of this study.At the time of enrollment,baseline data information is collected through questionnaires,body measurements,laboratory tests,and lung function tests.The c2 test was used to analyze the distribution of smoking behavior under different types of lung function injury.A linear correlation was used to analyze the correlation between smoking behavior and lung function indicators in smoking populations.Results: The average age of 6734 participants at baseline was 51.03±9.43 years,of which 2841 were males(42.19%)and 3893 were females(57.81%).6,374(94.65%) were married and 360(5.35%)were non-married;3,893(57.81%)lived in urban areas and 2,841(42.19%)lived in rural areas;2,302(34.20%)had an education level of primary school and below,4202(61.87%)had a junior high/high school level,and 229(3.40%)had a college/university level.The differences in the sex distribution of the above characteristics were statistically significant besides age(P<0.05).The FVC%,FEV1%,FEV1/FVC and PEF% of the total population were 0.94±0.29,0.67±0.22,0.84±0.21 and 0.79±0.26,respectively.Among the total study participants,3014(45.26%)had normal lung function,1428(21.21%)had restrictive lung function impairment,1871(27.78%)had obstructive pulmonary impairment,and 421(6.25%)had mixed lung function impairment.Under different types of lung function impairment,the smoking status of the total population,the smoking years of the smoking population and the number of smoking package year of the smoking population were significantly different(P<0.05).Taking people who are smoking(1707)as the study population,it was found that people who smoked for more than 30 years or smoke package year more than 30 accounted for the smallest proportion of people with normal lung function.There was a correlation between FVC,FVC,FEV1,FEV1,FEV1/FVC,PEF,PEF% and smoking years and smoking package year(P<0.05)Conclusion: Smoking status,years of smoking,and number of years of smoking packages all affect the distribution of types of lung function injuries in the population.The number of years of smoking and the number of years of smoking packages are closely related to the functional indicators of the lungs in the smoking population.The FVC%,FEV1%,FEV1/FVC and PEF% of the total population were 0.94±0.29,0.67±0.22,0.84±0.21 and 0.79±0.26,respectively.Among the total study participants,3014(45.26%)had normal lung function,1428(21.21%)had restrictive lung function injury,1871(27.78%)had obstructive pulmonary impairment,and 421(6.25%)had mixed lung function injury.Under different types of lung function injury,the smoking status of the total population,the smoking years of the smoking population,and the number of smoking packs were significantly different(P<0.05).Taking people who are smoking as the study population,it was found that people who smoked for more than 30 years,number of smoking package year of whom for was above 30 accounted for the smallest proportion of people with normal lung function.There was a linear relationship between FVC,FVC,FEV1,FEV1,FEV1/FVC,PEF,PEF% and smoking years and number of smoking package year(P<0.05).Part 3 A cohort study of smoking behavior and lung function status on the risk of cardiovascular diseaseObjective: To explore the effects of smoking behavior,lung function status,and the combination of the two on the risk of cardiovascular events and all-cause death.Methods: The subjects of the study are described in Part II.Follow-up was performed every 3 years after baseline enrollment,with follow-up outcomes including MACEs(stroke,myocardial infarction,and heart failure)and death,and the follow-up was completed in December 2018.MACEs(stroke,myocardial infarction,heart failure)and all-cause deaths during follow-up were calculated on a per-thousand person-year.The cox proportional risk model was used to analyze the effects of smoking behavior,lung function status,and the combination of the two factors on cardiovascular events and all-cause death.Hazard ratios(HRs)and 95% confidence intervals(CIs)were used to reflect the risk of cardiovascular events and all-cause death under different smoking behaviors,lung function conditions.Results: 6734 respondents were included in the final statistical analysis.The average follow-up time was 8.25 years,and the cumulative follow-up was 62,626 person-years.During the follow-up period,a total of 227 people had major cardiovascular events,with a total of 185 strokes,41 myocardial infarctions,and 5 heart failures.There were 46 cardiovascular deaths and 231 all-cause deaths,respectively.After adjusting for age and sex,the risk of MACEs and all-cause deaths in people with restrictive lung impairment was 1.455 times higher(HR=1.455,95% CI: 1.055-2.005)and 1.462 times higher(HR=1.462,95% CI: 1.038-2.059),and the risk of MACEs of people who smoking more than 30 years was 1.679 times that of smoking years less than 30 years(HR=1.679,95% CI: 1.112-2.535).After adjusting for all confounding factors,the increase of FVC,FVC%,FEV1,FEV1,FEV1/FVC,PEF%,PEF% per 1 unit will reduce the corresponding event risk.After adjusting for all confounding factors,the risk of stroke in people with restrictive lung function impairment was 1.484 times higher than that of people with normal lung function(HR=1.455,95% CI: 1.042-2.110);the risk of all-cause death in people with mixed lung function impairment was 1.915 times higher than that of people with normal lung function(HR=1.915,95% CI: 1.269-2.892).The risk of all-cause death of people smoking more than 30 years was 1.951 times that of smoking years less than 30 years(HR= 1.951,95% CI: 1.100-3.457)(P<0.05).Patients with both smoking years of more than 30 and abnormal lung function were 2.117 times more likely to die all-cause death than those with smoking year of less than 30 years and normal lung function(HR= 2.117,95% CI: 1.133-3.954).Conclusion: Functional indicators of the lungs,FVC,FEV,and PEF,all increase the risk of major cardiovascular events,stroke,and all-cause death.In smoking populations,smoking years are a major risk factor for an increased risk of major cardiovascular events,stroke and all-cause death.People with ≥30 years of smoking and abnormal lung function are more likely to increase the risk of cardiovascular events and death. |
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