Experimental Study Of The Therapeutic Effects Of N-acetylcysteine And Hydrocortisone On Severe Acute Pancreatitis

Objective To investigate the therapeutic effects and mechanisms of N-acetylcysteine(NAC) on severe acute pancreatitis (SAP).Methods Fifty-four SD rats were randomized into three groups: sham operation (SO)group, SAP group and NAC-pretreated group. The model of SAP was induced by retrograde injection of 5% sodium taurocholate into the bili-pancreatic duct in SD rats, NAC-pretreated group were given 200mg/kg NAC intraperitoneally 30 min before inducing SAP. Rats in the three groups were killed at 3,6,12 hours after induction of the model. The levels of amylase,malondialdehyde(MDA) in plasm, the myeloperoxidase(MPO) in the pancreas and lung, and the wet /dry ratio of lung were measured. The levels of plasm TNF-α,IL-6 were detected by enzyme linked immunosorbent assay (ELISA) , intrapulmonary TNF-α mRNA was detected by reverse transcript PCR (RT-PCR) . The histopathological changes of pancreatic and pulmonary tissue were evaluated.Results (1) Compared with SO group, the levels of plasm amylase,TNF-α,IL-6,MDA, the intrapancreatic and intrapulmonary MPO significantly increased in SAP group (P<0.05) , the expression of TNF-α mRNA in the lung significantly increased in SAP group (P<0.01), and the wet /dry ratio of lung also significantly increased in SAP group at 6h, 12h (P<0.01), the pancreas and lung injury were aggravated gradually. (2) Compared with SAP group, the levels of plasm amylase,TNF-α,MDA, intrapancreatic and intrapulmonary MPO, and the expression of TNF-α mRNA in the lung significantlydecreased in NAC-pretreated group at 3h,6h,12h (P<0.05) , the levels of plasm IL-6significantly decreased in NAC-pretreated group only at 3h,6h (P<0.05) ,the wet /dry ratioof lung and the pancreatic histopathologic scores significantly decreased inNAC-pretreated group at 6h,12h (PO.05), the severity of pancreas and lung injury alsosignificantly decreased in NAC-pretreated group.Conclusions Oxygen free radicals (OFR) ,TNF-a,IL-6 might play important role in thepathogenesis of SAP, NAC might have therapeutic effects on SAP by cleaning OFR anddecreasing the production of TNF-a,IL-6.Part two Experimental study of the therapeutic effects of hydrocortisone on severe acute pancreatitisObjective To investigate the therapeutic effects and mechanisms of hydrocortisone on severe acute pancreatitis(SAP).Methods Fifty -four SD rats were randomized into three groups: sham operation (SO) group, SAP group and hydrocortisone -treated group. The model of SAP was induced by retrograde injection of 5% sodium taurocholate into the bili-pancreatic duct in SD rats, hydrocortisone -treated group were given lOmg/kg hydrocortisone 10 min after inducing SAP. Rats in the three groups were killed at 3,6,12 hours after induction of the model. The levels of plasm amylase, intrapancreatic and intrapulmonary myeloperoxidase(MPO), and the wet /dry ratio of lung were measured, The levels of plasm TNF-a,IL-6 were detected by ELISA, the levels of plasm TXB2, 6-Keto-PGFia were detected by radioimmunoassay(RIA), the TXB2/6-Keto-PGFia was calculated. The histopathological changes of pancreas and lung were evaluated.Results (1) Compared with SO group, the levels of amylase,TNF-a,IL-6,TXB2 , TXB2/6-Keto-PGFiain plasm, the MPO in the pancreas and lung significantly increased in SAP group (PO.05 ) , the pancreatic histopathologic scores significantly increased in SAP group (P<0.01) , the wet /dry weight ratio of lung significantly increased in SAP group at 6h,12h (PO.01) , the pancreas and lung injury were aggravated gradually. (2) Comparedwith SAP group, the levels of plasm TNF-a,IL-6,TXB2TXB2/6-Keto-PGFia) intrapulmonary MPO significantly decreased in hydrocortisone-treated group at 3h,6h,12h (P<0.05) ,the wet /dry ratio of lung significantly decreased in hydrocortisone -treated group only at 6h,12h (PO.05) , and the severity of lung injury significantly decreased in hydrocortisone-treated group.But there were no difference between hydrocortisone -treated group and SAP group in the pancreatic histopathologic scores and the severity of pancreas injury.Conclusion Hydrocortisone might have therapeutic effects on SAP by decreasing the production of TXA2,TNF-a,IL-6.