The Effects Of H₂S And Its Synthetase Inhibitor?PAG? On The Impaired Autophagic Flux In Caerulein-induced Acutepancreatitis In Mice

Object:The present study was aimed to investigate the effect of H2S and PAG on the impaired autophagic flux in caerulein-induced acute pancreatitis in mice.Methods:60 male Balb/c mice,were randomly divided into 4 groups:control group,model group,the sulfur sodium hydride?NaHS?group,the PAG group.AP was induced in mice via hourly intraperitoneal injection of normal saline or saline containing caerulein?50ug/kg?for 6 hours in vivo.The experimental group rats were received of NaHS?10mg/kg?or PAG?100mg/kg?1h before the induction of AP and killed at 6h after the last injection of saline or Cn.Biochemical and histopathological changes were used to evaluate the severity of SAP.And the expression of LC3-II/LC3-I and P62 using western-blot method were uesd to evaluate autophagy pathway function.Results:1.Compared with the control group,the concentration of serum H₂S concentration and the expression of H₂S synthetase in pancreatic tissue of AP group were obviously higher.2.AP group significantly increased the activities of amylase,lipase,the levels of H₂S and the scores of pancreatic tissue pathologic grading compared with the normal control group.And all of the above index of AP group are much lower than NaHS but higher than PAG group.PAG can reduce the pancreas damage.3.The expression of LC3-II/LC3-I and P62 in AP group was increased compared with the normal control group,but lower than the NaHS group.After PAG intervention,The expression of those protein were decreased and the impaired autophagic flux was alleviated.Conclusions:1.The concentration of H₂S and its synthetase expression were increased in pancreatitis show that hydrogen sulfide was induced in pancreatitis.2.Exogenous H₂S can increase serum amylase and lipase levels,and aggravated pancreas damage.Inhibit hydrogen sulfide synthesis can reduce the levels of serum amylase,lipase,alleviated pancreatitis severity at the same time,Which has certain protective effect of pancreatitis.3.Hydrogen sulfide aggravates pancreatitis by aggravating autophagy pathway disorders.The protctive effect and therapeutic potential of Hydrogen sulfide synthetase inhibitors in the treatment of AP maybe associated with the improvement of autophagy flux.