The Characteristics Of Different Stages In Rat With Severe Acute Pancreatitis Immune Injury And The Effect Of Immune Modulators

Objective To observed the immune status- changes of different time in rats with severe acute pancreatitis,at the same time to observed the regulatory mechanism of NF-κB on dynamic changes and significances of TNF-α,IL-1βand ICAM-1 in severe acute pancreatitis(SAP) rat, and assess the effect of pretreatment with MMF(mycophenolate mofetil) on them.Method 96 male SPF level Wistar rat were randomly divided into normal group,sham group,SAP group,and MMF group. (1) normal group was just Abdominal incision then Suture(n=24); (2) sham operation group. sham-operated animals served as control. operation was executed, STC was not injected, but pancreas was flipped and striked gently five times(n=24); (3)SAP group was induced by the retrograde injection of sodium taurocholate (STC) in the pancreatic duct(n=24); (4)MMF group same as SAP group,but MMF(250mg/kg) was injected intraperitoneally one hours after to STC(n=24). Rats were killed by abdominal aorta exsanguination at 3h,6h,12h and 24h after the induction of pancreatitis. pancreatic histologic scroe were assessed and serum amylase (AMS),C-reactive protein (CRP),ALT (alanine aminotransferase),AST(aspartate aminotransferase),BUN (blood urea nitrogen),CREA (creatinine),CK (creatine kinase),LDH (lactate dehydrogenase) were measured by automatic biochemical detector, the concentration of inflammatory cyctokines (TNF-α,IL-1βand ICAM-1) of the blood were measured by ELISA,the pancreatic tissue expression of NF-κB mRNA were measured by Quantitative PCR.Results Compared with sham group,pancreatic histologic score,the indicator for responsed pancreatic injury like Serum AMS,CRP,responsed Liver function like ALT,AST,responsed Renal function like BUN,CREA,responsed Myocardial injury like CK,LDH; TNF-αIL-1βand ICAM-1 in SAP group were increased significantly (P<0.05), Pretreatment with MMF obviously deceased histologic score and the serum level of AMS,CRP,ALT,AST,BUN,CREA,CK,LDH, the level of TNF-αIL-1βand ICAM-1, NF-κB mRNA was higher than SAP group in early SAP (P<0.05).Conclusion The immune status of the rat with SAP can be divided into different periods like the immune pre-excitation,the immune excesses,the immune depletion,the immune recovery,cytokines play an important role in early progress of SAP; MMF could attenuate the severity of inflammatory response through inhibiting of cellular immunity and regulating the pro-inflammatory cytokines produced.