| 1. BackgroundAcute lung injury (ALI)/Acute respiratory distress syndrome (ARDS) are seen in patients with sepsis, severe trauma, fat embolism and so on Which are disorders marked by a significant inflammatory response to a local (pulmonary) or remote (systemic) insult resulting in injury to alveolar epithelial and endothelial barriers of the lung, acute inflammation and protein rich pulmonary edema. ARDS is the more severe form of ALL Considerable advances have been made in theunderstanding of the pathophysiology and pathology of ARDS. Clinicians are still faced with the challenge of managing this disease at present. Many support therapies have been developed, such as mechanical ventilation, but no specific pharmacological treatment has emerged which are capable of improving the outcome of patients with ARDS. The mortality of ARDS/ALI is still high (approximately 40%), despite recent advances in intensive care, because there are only a few drugs available for the prevention and treatment of ARDS/ALI. Therefore, the development of new available drugs against ARDS/ALI is very important.Lipopolysaccharide (LPS) causes acute lung injury associated with the increase in alveolar-capillary permeability, the activation of macrophages, neutrophil influx into the lungs, and parenchymal injury. This pulmonary response contributes to the pathogenesis of various acute inflammatory respiratory diseases. Nuclear factor-kappa B (NF-κB) are crucial in intracellular signal transduction, mediating cell responses to a variety of inflammatory stimuli, such as ultraviolet irradiation, LPS, bacterial or viral products, cytokines (TNF,IL-1 et al) and therapeutic drugs. NF-κ. B can regulate the expression of many genes involving in cytokines, chemokines, adhesion molecules, and apoptosis factor. In unstimulated cells, NF-κB in cytoplasm remains to be bound to the inhibitory molecule, IkB, which prevents it from entering the nuclei. When cells are stimulated, specific kinases phosphorylate IkB and cause its rapid degradation. The release of NF-κB from IkB results in NF-kB into the nucleus, where it binds to an enhancer of target genes and regulates the expression of many genes.Prostaglandin El has been demonstrated to reduce lung injury following ALI/ ARDS. The beneficial effect of PGE1 has been previously attributed to its vasodilative property, which likely leads to a better distribution of the preservation solution throughout acute lung injury. in addition, PGE1 may promote pulmonary protection by stimulating cyclic-3',5' adenosine monophosphate(cAMP)-dependent protein kinase during ALL cAMP-dependent protein kinase has been shown to reduce endothelial permeability and to prevent neutrophil adhesion and platelet aggregation.2. ObjectiveTo investigate LPS-induced ALI relation to NF-kB intracellular signaltransduction in rats and regulatory effect of PGE1 to NF-kB and cytokines, and illuminate the protection mechanism of PGE1 in ALI.3. Methods45 male S-D rats were randomly allocated into there groups: group A(normoal group,n=15), group B(LPS group,n=15) and group C(LPS +PGElgroup, n=15). We observed respiratory rate ,purple ,the changes of lung tissue, cell count and type in bronchoalveolar lavage fluid(BALF), IL-1β , TNF-α, IL-12 and IL-10 concentration in serum, and activity changes of NF-κB from the frozen lung tissue at lhr,2hrs and 4hrs after LPS was given I.P.4. Results1) The respiratory rate in the LPS group was obviously quicker than that in the normal group, and there was obviously purple in the LPS group. The respiratory rate and purple were lighter in PGEl+LPS group. Lung tissue was pink , without hyperemia and edema in the normal group, but in the LPS group, lung tissue was obviously hyperemia and edema, and hemorrhagic spots were found on the surface. Lung tissue was lightly hyperemia and edema in the PGE1+LPS group.2) Leukocytic total and percent of neutrophil in the LPS group increased more significantly than that in the normal group (P < 0.05) ,and it increased with time, while the percentage of macrophage signif...
|
PDF Full Text Request