| Objective:1. To investigate the effects of SO2(sulfur dioxide) on emergency hospital visits (EHVs) for stroke and further elucidate the seasonal differences.2. To estimate the effects of PbSO4(lead sulfate) on cell viability and RAS system in HUVEC.3. To study the effects of PbSO4on blood pressure and RAS system in SD rats, and discuss the role of ACEI in the process.Methods:1. The daily data of EHVs for stroke were gathered from the third Xiangya hospital during2008-2009. The corresponding meteorological information was also collected. The seasonal-stratified unidirectional case-crossover design with1:4matched pair was used to set up both single-pollution models and multi-pollution models for the data analysis.2. Cells (HUVEC) were randomly divided into4groups, including blank control group, low concentration group (PbSO40.17mg/ml), median concentration group (PbSO40.85mg/ml), high concentration group (PbSO44.25mg/ml). The dose of PbSO4was designed according to the literature and the lead concentrations in PM2.5. Each group was treated with corresponding doses of PbSO4for24hours. MTT assay was used to evaluate the changes of cell viability. RT-PCR and Western Blot were used to analyze both the mRNA and protein expression of ACE and AT1R, respectively. ELISA was used to determine the protein level of AngⅡ in the supernatant.3.24SD rats were divided into four groups, including control group, PbSO4group, PbSO4+Captopril group and Captopril group. In PbSO4+Captopril group and Captopril group, Captopril were given by intragastric administration at the dose of100mg/kg per day. In other two groups, the same dose normal saline were given. Three days later, PbSO4were given by intratracheal instillation at the dose of84μg/kg in PbSO4group, PbSO4+Captopril group, respectively. The dose of PbSO4was designed according to the literature and the lead concentrations in PM2.5of Changsha. The same dose of normal saline were given in control group and Captopril group. The blood pressure of rats were measured after24hours of instillation and then the rats were sacrificed immediately. ELISA was used to determine the protein level of AngⅡ and Ang(1-7) in the blood. RT-PCR and Western Blot were used to analyze both the mRNA and protein expression of ACE, AT1R, ACE2and Mas in myocardium and aorta, respectively.Results:1. After adjusting the meteorological factors (temperature and relative humidity) in single-pollution models, an10μg/m3increase of SO2were significantly associated with EHVs for total stroke, cerebral hemorrhage and cerebral infarction at lags of0,1,2and3days in autumn, respectively (OR>1). In multi-pollution models, an10μg/m3increase in SO2were significantly associated with EHVs for total stroke (OR=1.301,95%CI:1.038-1.631) and cerebral infarction (OR=1.446,95%C1:1.130-1.850) in autumn, respectively.2. After cells were exposed to PbSO4for24hours, the cell viability in three experimental groups were all lower than that in control group, but there was no statistical significance (P>0.05). The mRNA expression levels of ACE and AT1R in three experimental groups were all higher than that in control group, and there was statistical significance in median concentration group and high concentration group (P<0.05).The protein expression levels of AngⅡ and AT1R in three experimental groups were all higher than that in control group, and there was statistical significance in median concentration group and high concentration group (P<0.05). The protein expression of ACE in median concentration group and high concentration group were significantly higher than that in control group(P<0.05).3. PbSO4induced significant increase of diastolic blood pressure (P<0.05), and the effect could be significantly weaken by Captopril in SD rats (P＜0.05). Plasmic AngⅡ protein level and the expression of ACE and ATIR protein in myocardium and aorta significantly increased in PbSO4groups compared with those in control group (P＜0.05), but PbSO4had no significant effects on the plasmic Ang(1-7) protein and the expression of ACE2and Mas protein in myocardium and aorta (P>0.05). The effects of PbSO4on Ang Ⅱ and the expression of ACE and AT1R in myocardium and aorta could be significantly weaken by Captopril (P<0.05).Conclusion:1. The elevated concentration of SO2in autumn was closely related to increased EHVs for stroke, especially cerebral infarction.2. PbSO4could increase the expression of ACE-AngⅡ-AT1R axe genes in HUVEC cells.3. Acute exposure of PbSO4could increase diastolic blood pressure and the expression of ACE-AngⅡ-AT1R axe genes, which could be significantly weaken by Captopril. |
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