Abstract
BackgroundAcute lung injury (ALI) is an acute multifactorial infectious disease induced by trauma, pneumonia, shock, and sepsis. This study aimed to investigate the protective effects of pseudoephedrine and emodin combined treatment in experimental ALI, as well as the mechanisms underlying the regulation of inflammation and pulmonary edema via the VIP/cAMP/PKA pathway.MethodsThe wistar rats were randomly divided into fifteen groups (n = 5). Rats in each group were given intragastric administration 1 h before LPS injection. Those in the control and LPS groups were given intragastric administrations of physiological saline, rats in other groups were given intragastrically administered of differential dose therapeutic agents. The rats in the LPS and treatment groups were then injected intraperitoneally with LPS (7.5 mg/kg) to induce ALI. After being treated with pseudoephedrine and emodin for 12 h, all animals were sacrifice. Anal temperatures were taken on an hourly basis for 8 h after LPS injection. Pathological examination of lung specimen was performed by H&E staining. Cytokines (IL-1β, TNF-α, IL-6, iNOS, IL-10, Arg-1, CD86, CD206, F4/80, VIP) in lung tissue were assayed by ELISA and immunofluorescence. The expression of VIP, CAMP, AQP-1, AQP-5, p-PKA, PKA, p-IκBα, IκBα, p-p65, p65, p-P38, P38, p-ERK1/2, ERK1/2, p-JNK1/2, JNK1/2 protein in lung was determined by western blotting.ResultsAfter rats being treated with pseudoephedrine + emodin, reduced of fever symptoms. The contents of inflammatory cytokines (IL-1β, TNF-α, IL-6, iNOS) were decreased and anti-inflammatory cytokines (IL-10, Arg-1) were significantly increased in serum. Pseudoephedrine + emodin treatment effectively promoted VIP cAMP and p-PKA protein expression in lung tissues, and significantly inhibited NF-κB, MAPK phosphorylation, Pseudoephedrine + emodin treatment can inhibit M1 polarization and promoted M2 polarization via the VIP/cAMP/PKA signaling pathway.ConclusionsThe combination of Pseudoephedrine and emodin was effective in ameliorating LPS-induced ALI in rats by inducing VIP/cAMP/PKA signaling. Inhibiting the NF-κB, MAPK inflammatory pathway, relief of pulmonary edema suppressing macrophage M1 polarization, and promoting macrophage M2 polarization.
Highlights
Acute lung injury (ALI) is an acute multifactorial infectious disease induced by trauma, pneumonia, shock, and sepsis
The combination of Pseudoephedrine and emodin was effective in ameliorating LPS-induced ALI in rats by inducing Vasoactive intestinal peptide (VIP)/Cyclic adenosine monophosphate (cAMP)/Protein kinase (PKA) signaling
Pseudoephedrine + emodin inhibits the overexpression of inflammatory factors and promotes secretion of immunosuppressive factors Enzyme-linked immunosorbent assay (ELISA) was used to measure the expressions of common inflammatory and anti-inflammatory factors in rat bronchoalveolar lavage fluid (BALF) and serum to evaluate the effects of different drug concentrations and single-drug or combination treatments on the inflammation levels of ALI rats
Summary
Acute lung injury (ALI) is an acute multifactorial infectious disease induced by trauma, pneumonia, shock, and sepsis. ALI is characterized by inflammatory cell infiltration, massive production of inflammatory mediators, and diffuse lung inflammation [5]. It is recognized as one of the most direct causes of death in patients with sepsis, in which the intestinal barrier function is impaired and a large number of bacteria and endotoxins in the intestine invade the circulation through the portal vein and lymphatic system, thereby causing lung and intestinal infections and triggering multi-organ dysfunction syndrome [6, 7]. During the inflammation suppression stage, macrophages are typically polarized into M2 macrophages, which have anti-inflammatory repair functions and are typically induced by classical TH2 cytokines, such as IL-4, IL-10 and glucocorticoids
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