Protective effects of PAMAM dendrimers on acute pancreatitis induced by caerulin in mice: role of ma

来源 :International Conference for Physiological Sciences 2012(201 | 被引量 : 0次 | 上传用户:yinzhg01
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  Polyamidoamine (PAMAM) dendrimers of generation 5 (G5) has been widely used as carriers to deliver the therapeutic and diagnostic agents.However, the studies on the bioactivities of G5 carriers per se are inadequate, especially in their anti-inflammatory activities and the mechanisms.A caerulein-induced acute pancreatitis (AP)mouse model was used in this study to investigate the anti-inflammatory activities of the two G5 PAMAM dendrimers, negative-charged G4.5-COOH and neutralized G5-OH.Both of the two dendrimers significantly decreased the pathological changes of the pancreas and reduced the inflammatory infiltration of macrophages in the pancreatic tissues.G4.5-COOH, which showed better in vivo protective effects on AP than G5-OH, also dramatically decreased the release of amylase and lipase from pancreas into plasma.After the treatment of mice with G4.5-COOH or G5-OH, the expressions of pro-inflammatory cytokines in the pancreatic tissues were significantly inhibited, but the anti-inflammatory cytokines were not obviously influenced.The antiinflammatory mechanisms were proved in vitro in LPS-activated peritoneal macrophages.Our results indicated that the significant anti-inflammatory activities of G4.5-COOH and G5-OH PAMAM dendrimers were through the mechanisms of the deduction of the infiltration of macrophages in pancreas and the inhibition of the expressions of pro-inflammatory cytokines in activated macrophages.
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