Effect Of Hypothermia Induced By Adenosine5’-monophosphate And Recombinant High Density Lipoprotein On Inflammation Models Induced By LPS, Design And Synthesis Of PGG Derivatives

Inflammatory response is a common clinical pathological process. Largenumbers of studies show that inflammation associates with many diseases such ascardiovascular disease and tumors. Aimming at inflammatory response, both thehypothermia induced by5’-AMP and the effect of the constructed recombinant highdensity lipoprotein on the Lipopolysaccharide inflammatory models have beenstudied. Furthermore, penta-O-galloyl-glucosamine analogues have been designedand synthesized, anticipating to obtain targeting anti-arthritis compounds which havea relatively higher bioactivity.1. Building hypothermia with different concentrations of5’-AMP finds that at thedose of0.5g/kg, the rats’ body temperature can reduce to18℃and maintain morethan10hours. Detecting the inflammatory cytokine levels in the plasma andbronchoalveolar lavage fluid(BALF) use ELISA method, and analyze the pathologicalchanges in the lungs with hematoxylin-eosin staining method. The experiments resultsindicate that hypothermia has protective effects on inflammation induced by LPSwhich was demonstrated by the following results:1) a significant reduction of IL-1β(p<0.05), IL-6(p<0.05)and TNF-α (p<0.05) and an increase of IL-10(p<0.05)in theplasma and bronchoalveolar lavage fluid (BALF) levels in rats that are pre-treatedand post-treated with5’-AMP, when compared with the rats injected with LPS only;2)a significant inhibition of the acute lung injury induced by LPS.Purified rHDL74, rHDL228and rHDLwt are added to each group in RAW264.7inflammation model induced by LPS. Detecting the inflammatory cytokine levels in the culture medium use ELISA method, and analyze the changes of key enzymes ofinflammatory signaling pathways with western blot method. Experimental datasuggest that rHDL74exhibits higher anti-inflammation by significant reduction ofIL-6(p<0.05) and TNF-α (p<0.05) levels in the culture medium and inhibiting theactivation of JNK and p38. While rHDL228has hyper-proinflammation effectdemonstrated by increasing IL-6(p<0.05) and TNF-α (p<0.05) levels and aggravatingthe activation of ERK.2.1,2,3,4,6-penta-O-galloyl-β-D-glucose(PGG) is a natural compound containedin several medicinal herbals and Arctic seaweeds. PGG has become a hot researchfocus with many attractive pharmacologic and physiologic activities such asanti-tumor activity, anti-diabetic activity, antivirus and antibacterial activities,anti-allergy activity and anti-inflammation activity. Based on the skeletion ofglucosamine, structure modification of PGG natural products has been done.Consequently, two compounds which have not been reported by references have beenobtained, namely, penta-O-galloyl-glucosamine and2-O-galloyl-glucosaminerespectively. Moreover, optimization has been done on the synthetic route of theanalogues of PGG with the skeleton of glucosamine.