H2 S regulates severe acute pancreatitis through PI3K/AKT-NF-κB pathway / 重庆医学

ABSTRACT

Objective To explore the role and mechanism of H2 S in severe acute pancreatitis .Methods SD rats were randomly assigned into several experimental groupscontorl group(n=6) ,SAP group(n=10) ,PAG+SAP group(n=10) ,5 mg/kg NaHS+SAP group(n=10) ,10 mg/kg NaHS+SAP group(n=10) ,20 mg/kg NaHS+SAP group(n=10) ,100 mg/kg NaHS+SAP group (n=10) ,wortmannin(W)+ SAP group(n= 10) ,5 mg/kg NaHS + W+ SAP group(n=10) and 100 mg/kg NaHS+ W+ SAP group(n=10) .These rats were intra-peritoneal injected L-Arginine to get SAP model ,and sacrificed ar 24 h hour after the first in-jection .Plasma IL-6 and MPO activity in pancreas were determined by ELISA .Expression of p-AKT and IκBαin pancreas were de-tected by Western blot ,and NF-κB activity was assessed with EMSA .Results SAP and PAG+ SAP resulted in a significant in-creasing in plasma IL-6 ,MPO activity and expression of p-AKT in pancreas ,when compared with the control group(P<0 .05) ,and NF-κB activity also increased ,and NF-κB activity in PAG+SAP group was more significant (P<0 .05);however ,IκBαexpression in SAP and PAG+SAP down-regulated obviously ,when compared with the control group(P<0 .05) ,and the expression in PAG+SAP group was significantly lower(P<0 .05) .Different dosage of NaHS reduced that the level of plasma IL-6 ,MPO activity ,ex-pression of p-AKT and NF-κB activity in pancreas changed in different degrees ,yet IκBαexpression in these groups increased gradu-ally .When compared with the SAP group ,5 mg/kg NaHS+SAP and 100 mg/kg NaHS+SAP ,plasma IL-6 ,MPO activity and ex-pression of p-AKT in pancreas significantly depressed after given wortmannin ,besides NF-κB activity also down-regualated;never-theless IκBαexpression up-regulated .Conclusion H2 S in precondition induced the development of an anti-inflammatory activity in SAP ,and in proportion with the concentration of H2 S in blood in a degree .H2 S regulated the degree of SAP injury via PI3K/AKT-NF-κB pathway .