RESUMO
Objective: Myocardial ischemia/reperfusion (MI/R) injury is a major cause of cardiac tissue damage, with high disability and death rates. Although both dexmedetomidine (Dex) and propofol (PPF) have been indicated to alleviate MI/R injury in rat models, the effects of the combined use of these two drugs remain unclear. This study aimed to investigate the combined effects of Dex and PPF against MI/R injury and related mechanisms. Methods: A rat model of MI/R injury was established and used to explore the combined effects of Dex and PPF on MI/R injury. Hematoxylin-eosin (HE) and Masson staining were used for histopathological evaluation. 2,3,5-triphenyltetrazolium chloride (TTC), echocardiography, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining were used to determine myocardial infarction size, cardiac function, and apoptosis, respectively. Enzyme-linked immunosorbent assay (ELISA) was performed to assess myocardial function and oxidative stress (OS). Autophagy was observed through transmission electron microscopy. Moreover, western blotting was conducted to detect autophagy markers and the AMPK pathway. Results: The combination of Dex and PPF alleviated histopathological injury, reduced myocardial infarction, and rescued cardiac dysfunction in MI/R rats. Furthermore, Dex combined with PPF decreased the levels of MDA and ROS and increased the SOD level in MI/R rats. Besides, Dex combined with PPF inhibited myocardial apoptosis in MI/R rats. After combined treatment with Dex and PPF, the number of autophagosomes, expression levels of Beclin-1 and LC3II/LC3I were elevated, while the expression levels of p62 were reduced in MI/R rats. The combined use of Dex and PPF activated the AMPK pathway in MI/R rats. Compound C (an AMPK inhibitor) could abolish the combined effects of Dex and PPF on alleviating myocardial injury and enhancing autophagy in MI/R rats. Conclusion: The combination of Dex and PPF attenuated MI/R injury in rats, which may be associated with the activation of the AMPK signaling pathway.
RESUMO
To develop effective mitigation policies, a comprehensive understanding of the evolution of the chemical composition, formation mechanisms, and the contribution of sources at different pollution levels is required. PM2.5 samples were collected for 1 year from August 2016 to August 2017 at an urban site in Zibo, then chemical compositions were analyzed. Secondary inorganic aerosols (SNA), anthropogenic minerals (MIN), and organic matter (OM) were the most abundant components of PM2.5, but only the mass fraction of SNA increased as the pollution evolved, implying that PM2.5 pollution was caused by the formation of secondary aerosols, especially nitrate. A more intense secondary transformation was found in the heating season (from November 15, 2016, to March 14, 2017), and a faster secondary conversion of nitrate than sulfate was discovered as the pollution level increased. The formation of sulfate was dominated by heterogeneous reactions. High relative humidity (RH) in polluted periods accelerated the formation of sulfate, and high temperature in the non-heating season also promoted the formation of sulfate. Zibo city was under ammonium-rich conditions during polluted periods in both seasons; therefore, nitrate was mainly formed through homogeneous reactions. The liquid water content increased significantly as the pollution levels increased when the RH was above 80%, indicating that the hygroscopic growth of aerosol aggravated the PM2.5 pollution. Source apportionment showed that PM2.5 was mainly from secondary aerosol formation, road dust, coal combustion, and vehicle emissions, contributing 36.6%, 16.5%, 14.7%, and 13.1% of PM2.5 mass, respectively. The contribution of secondary aerosol formation increased remarkably with the deterioration of air quality, especially in the heating season.
