| Objectives:To investigate the effect of Hemin which induces endogenous HO-1 in panreas and kidney of rats model of SAP. Further we demonstate the protective effect of the overexpression of HO-1, which was induced by Hemin, on SAP and related renal injury and it's mechanism.Methods:Fourty-eight SD rats were randomly allocated into four groups: Sham operation group,Control group,Hemin group and ZnPP+Hemin group. We established the rats model of SAP by the operation of retrograde cannulation of the choledochus and pancreatic duct with 3％Sodium Cholate. The rats of Hemin group were intraperitoneally injected with hemin solution(30mg/kg). After 12h they were established to become model of SAP by the operation above. The rats of ZnPP+Hemin group were intraperitoneally injected with ZnPP solution(5ml/kg) 24h before the operation. They were intraperitoneally injected with hemin solution(30mg/kg) 12h before the operation. And then they were operated to become model of SAP. After the operation the rats were put to death in batch at the point of 3h,12h,24h. To compare pancreas' and kidneys' histological changes of each group by HE staining. To measure the expression of HO-1 and NF-κB/P65 in kidneys and pancreas by immunohistochemistry. To examine serum amylase,Cr,BUN. To measure the content of TNF-αin serum by ELISA. All data were demonstrated by (?)±SD. Statistical analysis was performed by SPSS 12.0. Every group was compared with each other by analysis of LSD-t,Kruskal-Wallis H or SNK-q. The results had statistical significance when P＜0.05.Results:The expression of HO-1 in pancreas and kidney of Sham operation group rats was equally low level expression. But compared with Sham operation group, the expression of NF-κB/P65 of Control group rats was significantly increased(P＜0.05)with time dependence. The histological changes of pancreas and kidney were deteriorated. The serum amylase,BUN,Cr,TNF-αwere significantly increased with time dependence. Compared with Control group, the expression of HO-1 in pancreas and kidney of the Hemin group rats was remarkable elevated with time dependence. At the same time the histological changes of pancreas and kidney were improved. Although the serum amylase,BUN,Cr,TNF-αand the expression of NF-κB/P65 of Control and Hemin group rats were significantly strenthened with time dependence, all these indexes of Hemin group were remarkable down-regulated compared with Control group at the same time. Compared with Hemin group, the expression of HO-1 in pancreas and kidney in ZnPP+Hemin group rats was remarkable reduced at the same time. The histological changes of pancreas and kidney were deteriorated. Although the serum amylase,BUN,Cr,TNF-αand the expression of NF-κB/P65 of Hemin and ZnPP+Hemin group rats were significantly strenthened with time dependence, all these indexes of ZnPP+Hemin group were remarkable upreguated compared with Hemin group at the same time.Conclutions:1. HO-1 is overexpressed with time dependence in pancreas and kidney by Hemin. Protection is mediated by HO-1-overexpressing tissues since hemin-primed tissues to the pancreas and kidneys after transfer to naive rats. 2. Hemin-activated overexpression of HO-1 in renal and pancreatitic tissues may offer novel therapeutic approaches for preventing severe acute pancreatitis and its renal complication. The mechanism of the protection is partly related to the HO-1's effect of reducing serum TNF-αand antiinflammation. 3. Hemin-activated overexpression of HO-1 in SAP rats protects from servere acute pancreatitis and its renal injury. The effect of antiinflammation may have certain association with the suppression of signal transduction of NF-κB.
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