ABSTRACT
ABSTRACT: Introduction: Intestinal flora and the translocation of its products, such as muramyl dipeptide (MDP), are common causes of sepsis. MDP is a common activator of the intracellular pattern recognition receptor NOD2, and MDP translocation can cause inflammatory damage to the small intestine and systemic inflammatory responses in rats. Therefore, this study investigated the effects of MDP on the intestinal mucosa and distant organs during sepsis and the role of the NOD2/AMPK/LC3 pathway in MDP-induced mitochondrial dysfunction in the intestinal epithelium. Methods: Fifty male Sprague Dawley rats were randomly divided into five treatment groups: lipopolysaccharide (LPS) only, 1.5 and 15 mg/kg MDP+LPS, and 1.5 and 15 mg/kg MDP+short-peptide enteral nutrition (SPEN)+LPS. The total caloric intake was the same per group. The rats were euthanized 24 h after establishing the model, and peripheral blood and small intestinal mucosal and lung tissues were collected. Results: Compared to the LPS group, both MDP+LPS groups had aggravated inflammatory damage to the intestinal mucosal and lung tissues, increased IL-6 and MDP production, increased NOD2 expression, decreased AMPK and LC3 expression, increased mitochondrial reactive oxygen species production, and decreased mitochondrial membrane potential. Compared to the MDP+LPS groups, the MDP+SPEN+LPS groups had decreased IL-6 and MDP production, increased AMPK and LC3 protein expression, and protected mitochondrial and organ functions. Conclusions: MDP translocation reduced mitochondrial autophagy by regulating the NOD2/AMPK/LC3 pathway, causing mitochondrial dysfunction. SPEN protected against MDP-induced impairment of intestinal epithelial mitochondrial function during sepsis.
Subject(s)
Acetylmuramyl-Alanyl-Isoglutamine , Intestinal Mucosa , Mitochondria , Nod2 Signaling Adaptor Protein , Rats, Sprague-Dawley , Animals , Acetylmuramyl-Alanyl-Isoglutamine/pharmacology , Male , Rats , Mitochondria/metabolism , Mitochondria/drug effects , Nod2 Signaling Adaptor Protein/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , Cytokines/metabolism , Lipopolysaccharides/toxicity , Sepsis/metabolism , Interleukin-6/metabolism , Microtubule-Associated Proteins/metabolism , Inflammation/metabolism , Reactive Oxygen Species/metabolismABSTRACT
In order to compare aerosol water-soluble inorganic species in different air-pollution periods, samples of PM10, PM2.1, PM1.1 and the main water-soluble ions (NH4+, Mg2+, Ca2+, Na+, K+, NO2(-), F(-), NO3(-), Cl(-), SO4(2-)) were measured, which were from 3 air-pollution incidents (continued pollution in October 16-30 of 2009, sandstorm pollution in April 27-30 of 2010, and crop burning pollution in June 14 of 2010. The results show that aerosol pollution of 3 periods is serious. The lowest PM2.1/PM10 is only 0.27, which is from sandstorm pollution period, while the largest is 0. 7 from crop burning pollution period. In continued pollution periods, NO3(-) and SO4(2-) are the dominant ions, and the total anions account for an average of 18.62%, 32.92% and 33.53% of PM10, PM2.1 and PM1.1. Total water-soluble ions only account for 13.36%, 23.72% and 28.54% of PM10, PM2.1 and PM1.1 due to the insoluble species is increased in sandstorm pollution period. The mass concentration of Ca2+ in sandstorm pollution period is higher than the other two pollution periods, and which is mainly in coarse particles with diameter larger than 1 microm. All the ten water-soluble ions are much higher in crop burning pollution especially K+ which is the tracer from crop burning. The peak mass concentrations of NO3(-), SO4(2-) and NH4+ are in 0.43-0.65 microm.
