The Effect Of Endogenous Hydrogen Sulfide Associated With TGF-?1/Smad7 Signaling Pathway In The Pancreatic Fibrosis Rat Model

ObjectiveTo investigate the influence of hydrogen sulfide on the TGF-b1/Smad7 signaling pathway and to clarify their effects on development of pancreatic fibrosis in rat.MethodsForty-eight Wistar male rats were randomly divided into four groups:normal control group?n=12?,model group?n=12?,NaHS group?n=12?and PAG group?n=12?.The model group?NaHS group and PAG group were given 10%DDC700mg/Kg by intraperitoneal injection every other day;NaHS group were given sodium hydrosulfide?56umol/L?,an H₂S honor,by intraperitoneal injecttion one time every day;PAG group were given DL-propargylglycine?45umol/L?,cystathionine-?-lyase inhibitor,by intraperitoneal injection one time every day.The normal control group and model groups were given an equal volume of saline solution.The general condition of rats were observed during the experiment every day.All mice were killed on the 30^th days.Plasma H₂S level was measured.Stained preparation of pancreatic tissue was executed with H&E and Masson method,histopathological score and collagen area percentage were measured.Preparation of pancreas tissue homogenates,Collagen I?Collagen III and TGF-b1 were detected by Elisa method,Smad7 were determined by Western blotting,The pancreas mRNA expression level of CSE was detected by real-time fluorescence quantitative RT-PCR.Results?1?The same point in time,Compared with the control group,Histological damage score and collagen area were significant higher in the model group?NaHS group and PAG group?p<0.05?;the model group were significant higher than the NaHS group?p<0.05?;the PAG group were significant higher than the model group?p<0.05??2?the level of Collagen I?Collagen III and TGF-b1 were significant higher in the model group?NaHS group and PAG group than the control group?p<0.05?;the model group were significant higher than the NaHS group?p<0.05?;the PAG group were significant higher than the model group?p<0.05?.?3?The expression of Smad7 was significant higher in the control group than the model group?NaHS group and PAG group?p<0.05?;the NaHS group was higher than the model group?p<0.05?;the model group was significant higher than the PAG group?p<0.05?.?4?The pancreas tissue expression of CSEmRNA and the level of serum H₂S in the NaHS group was significant higher than the control group?model group and PAG group?p<0.05?;the control group was significant higher than the model group?p<0.05?;the model group was significant higher than the PAG group?p<0.05?.ConclusionEndogenous H₂S was closely related with DDC induced pancreatic fibrosis in rat and had a notable anti-inflammatory and anti-fibrosis effect,moreover,H₂S can up-regulate the expression of Smad7 and down-regulate the expression of TGF-b1 in pancreatic fibrosis,which was possibly related to the up-regulation of TGF-b1/Smad7 signal pathway.