Role Of P38 Mitogen-activated Protein Kinase In Hypocalcaemia Of Rats With Severe Acute Pancreatitis

Objective To investigate the role of p38 mitogen-activated protein kinase(MAPK) signal transduction pathway in hypocalcaemia and parathyroid hormone receptor 1 (PTHR1) of rats with severe acute pancreatitis (SAP). Methods Seventy-two male health adult Sprague-dawley rats were completely randomized into three groups:SAP group,SAP treated with SB203580 group (SB group),sham operation group(SO group).SAP model was induced by bili-pancreatic duct retrograde infusion with 5% sodium taurocholate solution.In the SB group,rats were treated with the specific inhibior (SB203580) of p38MAPK 30 minutes before the induction of SAP model. Rats in each group were killed at 3h,6h,12h after operation to determine the Serum calcium, the change of phosphorylated p38MAPK and tumor necrosis factor (TNF)-alpha (by western blot) and the expression of PTHR1mRNA(by quantitative real-time RT-PCR),8 rats in each time point.Results Compared with sham group,the expression of bone phosphorylated p38MAPK and TNF-alpha were increased significantly,the mRNA level of bone PTHR1 down-regulated significantly and the concentration of serum calcium decreased significantly in SAP group.Compared with SAP group,the expression of bone phosphorylated p38MAPK [3h:(0.20±0.05)vs.( 0.40±0.06),t=-7.044,P=0.000;6h:(0.33±0.05)vs.(0.80±0.06),t=-18.099,P=0.000;12h:(0.27±0.05)vs.(0.51±0.03),t=-12.385,P=0.000] and TNF-alpha [3h:(0.31±0.03)vs.(0.70±0.03),t=-23.870,P=0.000;6h:(0.44±0.03)vs.(0.91±0.04),t=-27.755,P=0.000;12h:(0.37±0.04)vs.(0.80±0.03),t=-23.652,P=0.000] were decreased significantly, the mRNA level of bone PTHR1 [3h:(0.53±0.03)vs.( 0.28±0.03),t=17.858,P=0.000;6h:(0.44±0.06)vs.( 0.23±0.04),t=8.804,P=0.000;12h:(0.40±0.11)vs.( 0.20±0.03),t=5.060,P=0.001] up-regulated significantly and the concentration of serum calcium [3h:(2.39±0.06) mmol/L vs.( 2.31 ±0.06) mmol/L,t=2.900,P=0.012;6h:(2.35±0.10) mmol/L vs.( 2.11±0.06) mmol/L,t=5.507,P=0.000;12h:(2.26±0.12) mmol/L vs.( 2.01±0.04) mmol/L,t = 5.881,P = 0.000] increased significantly in SB group.Conclusion P38MAPK signal transduction pathway may mediates the development of hypocalcaemia,the level of serum calcium could be increased by blocking this pathway in rats with SAP.