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Acta Cirurgica Brasileira
0000-00-00 00:00:00

Glycogen synthase kinase-3 beta inhibitors protectagainst the acute lung injuries resulting from acute necrotizing pancreatitis

Descrição: Abstract Purpose The research is intended for clarification of the efficacy as well as the underlying mechanism of GSK-3- inhibitors on the advancement of acute lung injuries in acute necrotizing pancreatitis (ANP) in rats. Methods Seventy-two rats were randomly divided into 6 groups: (1)ANP-vehicle; (2)ANP-TDZD-8;(3)ANP-SB216763;(4)Sham-vehicle;(5)Sham-TDZD-8;(6)Sham-SB216763; Blood biochemical test, histopathological examination and immunohistochemical analysis of rats pancreas and lung tissues were performed. The protein expression of GSK-3-, phospho-GSK-3- (Ser9), iNOS, ICAM-1, TNF--, and IL-10 were detected in lung tissues by Western-blot. Results The outcomes revealed that the intervention of GSK-3- inhibitors alleviated the pathological damage of pancreas and lung (P<0.01), reduced serum amylase, lipase, hydrothorax and lung Wet-to-Dry Ratio, attenuated serum concentrations of IL-1- and IL-6 (P<0.01), inhibited the activation of NF--B, and abated expression of iNOS, ICAM-1 and TNF-- protein, but up-regulated IL-10 expression in lung of ANP rats (P<0.01). The inflammatory response and various indicators in ANP-TDZD-8 groups were lower than those in ANP-SB216763 groups. Conclusions Inhibition of GSK-3- weakens acute lung injury related to ANP via the inhibitory function of NF--B signaling pathway. Different kinds of GSK-3- inhibitors have different effects to ANP acute lung injury.

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