The Effect Of Taurine To P38 Mitogen Activated Protein Kinase Signaling Pathway In The Kupffer Cells From Severe Acute Pancreatitis Rats

AIM The rats were pretreated by taurine before the SAP model induced, then the kupffer cells were islolated by in situ perfusion with combine enzyme. The activity of P38 mitogen activated protein kinase (P38MAPK)and Nuclear factor-kappaB(NF-κB) in kupffer cells were detected, in order to investigate the effect of taurine to P38 mitogen activated protein kinase signaling pathway and pro-inflammatory cytokines, tumor necrosis factor-a(TNF-α) and intedeukin-lβ(IL-lβ) in the kupffer cells(KCs), in severe acute pancreatitis (SAP) rats.MEHTODS Sprague-Dwaley rats were randomized into three groups:①sham operation rats(SO group),②SAP rats(SAP group),③SAP rats given the taurine(Tau group). The SAP model was induced by the bili-pancreatic duct infusion with 5%sterile soduim taurocholate solution. The Tau group was injected taurine through vena caudalis at 24h,12h before the SAP model induced, other groups were given equal normal sodium. Rats from each group were killed at 12h,24h after sham operation or SAP. The serum transaminase and amylase levels were detected. Then KCs of every groups were isolated. The P38 MAPK activity (by Western blot analysis and immunocytochemical method) and the NF-κB activity (by electrophoretic mobility analysis) in KCs were examined. The levels of TNF-αand IL-lβin supernatant were determined by ELISA.RESULTS①In SAP group, the manifestation was like with that of severe acute pancreatitis, the serum transaminase and amylase levels in SAP group were highest(734.25±64.25 U/L,308.75±31.50 U/L,916.75±143.64 U/L and 865.75±86.19 U/L,368.13±35.88 U/L,1136.75±201.15 U/L), significantly higher than that of SO group(198.48±24.50 U/L,75.13±16.60 U/L,303.75±42.55 U/L and 286.46±28.32 U/L 109.50±24.40 U/L,368.88±74.81 U/L)(P<0.01), but in Tau group, were lower than that of SAP group(413.70±50.65 U/L,189.68±23.81U/L,560.25±85.14 U/L and 530.75±50.50 U/L,241.13±26.67 U/L 757.27±116.75 U/L)(P<0.05).②Although the protein of P38 MAPK were no significant difference in three groups (P>0.05),the phosphorylation of P38 MAPK in SAP group were highest(0.9852±0.0897 and 1.0315±0.0916), higher than that of SO group(0.6438±0.0215 and 0.7214±0.0484)(P<0.01),in Tau group the phosphorylation of p38 MAPK were lower than that of SAP group(0.7713±0.0819 and 0.8835±0.0685)(P<0.05).③The activity of NF-κB in SAP group were highest at every tim(e224.28±22.67 and 285.47±46.65),that in SO group were lowest(148.63±17.44 and 153.61±11.07), there was significantly difference between them(P<0.01),after pretreated by taurine in Taur group the activity were lower than that of SAP group(185.93±16.59 and 206.12±18.66)(P<0.01).④The protein expressions of TNF-αand IL-lβin supernatant were highest in SAP group at every time(885±156.7 ug/L,798±143.7 ug/L and 1068±241.5 ug/L,971±203.1 ug/L), it was higher than that in SO group(201±34.8 ug/L,247±48.4 ug/L and 238±51.4 ug/L,431±61.2 ug/L)(P<0.01),but in Tau group, the protein expressions of TNF-αand IL-lβwere obviously decreased contrasted to that of SAP group(551±176.5 ug/L,547±56.8 ug/L and 846±208.7 ug/L,724±142.6 ug/L)(P<0.05).⑤The phosphorylation of P38MAPK in KCs by immunocytochemical image analyse: the phosphorylation of P38MAPK in SAP group were highest(0.46±0.07 and 0.52±0.04), significantly higher than that of SO group(0.15±0.03 and 0.18±0.05)(P<0.01), but in Tau group, the value were decreased (0.25±0.03 and 0.30±0.08), it was statistical significance comparison to that of SAP group(P<0.05).CONCLUSION The activity of P38MAPK and NF-κB were inhibited by taurine, accrodingly the pro-inflammatory cytokines, TNF-αand IL-lβwere decreased significantly.Taurine can inhibite the inflammatory cytokines after SAP, and relieve the damage of liver in SAP. Taurine may be a potential drug in prevention and treatment of SAP.