Studies Of The Molecular Mechanisms In The Development And Progression Of Ischemic Stroke Induced By SO₂ Inhalation

With the development of industrialization, air pollution has been a serious threat to the health of human being. A large number of epidemiological literatures show an association between air pollution and ischemic stroke, and the effective pollutants may include SO2, NOx, O3, CO and particulate matter. With coal as the main energy resources in developing countries, SO2 has become the major pollutant, of which the toxicology effects have been paid more attention than other pollutants. However, the correlation and molecular mechanisms of air SO2 pollution and respiratory diseases were reported by many literatures, while relevant evidences between SO2 pollution and stroke are only seen in epidemiological studies. In order to make up the lack of accurate laboratory data about the relationship between SO2 and ischemic stroke, we designed the present study. Firstly, we treated healthy Wistar rats with SO2 at various concentrations, and used Real-time RT-PCR and Western-blot techniques to determined mRNA and protein expression of the stroke-related factors including endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and intercellular adhesion molecule-1 (ICAM-1) in the cortex, heart and lung. The results show that SO2 elevated the levels of ET-1, iNOS, COX-2 and ICAM-1 mRNA and protein in a concentration-dependent manner. The mRNA expression of TNF-a, IL-1β, iNOS, ICAM-1 in heart and lung show the same trend, which suggests a possible signaling pathway of ischemic stroke induced by SO2 through cardiopulmonary bypass. The release of pro-inflammatory factors in lung and heart into blood causes endothelial dysfunction of vascular and inflammation of brain, finally leads to cerebral infract. To confirm the hypothesis, we further set up rat model of ischemic stroke using middle cerebral artery occlusion (MCAO), and treated the model rats with filtered air and lower concentration SO2 for the same period. As expected, elevated expression of ET-1, iNOS, COX-2 and ICAM-1 occurred in the cortex of MCAO model rats exposed to filtered air, followed by increased activation of caspase-3 and cerebral infarct volume. Interestingly, SO2 inhalation after MCAO significantly amplified above effects, suggesting SO2 inhalation contributed to development of ischemic stroke. This article proved that exposure to SO2 contributed to the development and progression of ischemic stroke.