The Therapeutic Effect Of SDR5-Fc On Rat Model Of Severe Acute Pancreatitis

Background:Severe acute pancreatitis(SAP)progress quickly,high mortality rates and more complications,the pathogenesis of complex,brings the global great economic burden,pathogenesis theory mainly includes the pancreatic enzyme on its own,pancreatic acini circulation theory,theory of calcium overload,pancreas inflammation factor theory,theory of intestinal bacterial translocation in theory,the theory of apoptosis,oxidative stress,etc.,theory is the key pathogenesis of inflammation factor,work together to produce a variety of inflammatory medium inflammation cascade amplification effect,thus induce systemic inflammatory response syndrome(SIRS)causing multiple organ dysfunction syndrome(MODS)in patients died.Tumor necrosis factor Related Apoptosis Inducing Ligand(TRAIL)can induce Apoptosis by combining with Death Receptor(DR)in cells or tissues,and TRAIL combined with DR5 can not only mediate Apoptosis,but also conduct NF-?B Pathway,the production of interleukin-1beta(IL-1),interleukin-6(IL-6)and Tumor Necrosis factor-alpha(TNF-?)mediated inflammatory response.NF-?B is a key transcription Factor that regulates immunity and inflammation in SAP,TRAIL mainly has five death receptors,including TRAIL and DR5 highest affinity,natural with Soluble DR5(Soluble DR5)exist,s DR5 combined with TRAIL can only can't block signal further TRAIL mediated inflammatory response.Objective:Due to lack of effective drug treatment,SAP treatment has always been a difficult problem,now the treatment of SAP is limited to fasting,gastrointestinal decompression inhibition of pancreatic enzyme secretion analgesia spasmolysis,microcirculation improvement,organ function,maintenance and other symptomatic support therapy as a result,searching for new and more effective treatment is very important in this study through the establishment of SAP model in rats,To investigate whether s DR5-Fc has therapeutic effect on rat model of severe acute pancreatitis.Methods:There were 25 male SD rats,aged 6-8 weeks,200-220 g,with intact skin and hair,and relatively agile body response.Model 1 week before,in the ordinary grade clean room adaptive breeding,animal housing environmental requirements: the temperature is 20 to 25 ?,humidity is 50-10%,light/dark cycle time is 12 hours,well ventilated,able to give enough water and feed supply,ensure that every interval of 2 to 3 days change a bedding,feed,water,feeding cage and bedding are after high pressure sterilization.During the feeding period,the rats had no disease and died,and their living condition was good.They were randomly divided into 5 groups: normal group,model group,Ig G group,low-dose s DR5-Fc group,and high-dose s DR5-Fc group,with 5 mice in each group.Control group(NC group): two intraperitoneal injections of 0.9% normal saline at an interval of 1 hour;Model group(SAP group): 10% L-arginine(300mg/kg)was intraperitoneally injected twice at an interval of 1 hour to establish the SAP model of rats.Ig G group: after SAP model was successfully established for 30 min,Ig G was injected through rat tail vein.Low-dose s DR5-Fc group(Dex-L group): after the SAP model was successfully established for 30 min,the injection dose of s DR5-Fc of 7.5mg/kg was given through rat tail vein.High-dose s DR5-Fc group(Dex-H group): after the SAP model was successfully established for 30 min,s DR5-Fc of 15mg/kg was injected through rat tail vein.After the final injection of l-arginine solution,the time started to count as the successful time of modeling.24 hours after the modeling,blood was collected from the carotid artery of the rats,and part of the whole blood was tested by automatic blood cell analyzer for white blood cell count(WBC).Part of the product was put into the green heparin anticoagulation tube and centrifuged at 3000 rpm at 4? for 10 min.The supernatant was carefully absorbed and packed into the EP tube.The serum was separated and made.The levels of c-reactive protein(CRP),serum amylase(AMY),pancreatic amylase(PAMY),lipase(LIP)and blood calcium were detected by automatic biochemical analyzer at 200 ul.Results :(1)The rat model of severe acute pancreatitis was established successfully.(2)The WBC level in rats was measured by animal blood cell analyzer,and Ig G group and SAP group were significantly higher than NC group(p<0.05),there was no significant difference in WBC level between Ig G group and SAP group(P>0.05),The WBC level in Dex-H group decreased significantly in Dex-L group compared with SAP group(p<0.05),the dex-h group decreased more significantly(p<0.05);(3)The automatic biochemical analyzer was used to measure the AMY,PAMY,LIP and CRP in rats,and it was found that the Ig G group and SAP group were significantly higher than NC group(p<0.05),there was no significant difference in AMY,PAMY,LIP and CRP levels between Ig G group and SAP group(p>0.05)compared with the SAP group,the levels of AMY,PAMY,LIP and CRP in the Dex-L group and Dex-H group decreased significantly(p<0.05),the dex-h group decreased more significantly(p<0.05);(4)The serum calcium levels in rats were determined by automatic biochemical analyzer,and it was found that Ig G group and SAP group significantly decreased compared with NC group(p<0.05),there was no significant difference in serum calcium level between IgG group and SAP group(p>0.05),compared with SAP group,the serum calcium level of Dex-l group and Dex-H group was significantly increased(p<0.05),the increase of Dex-H group was more significant(p<0.05).Conclusions:According to the levels of WBC,CRP,serum calcium,AMY,PAMY and LIP,sdr5-fc has a certain therapeutic effect on the rat model of severe acute pancreatitis,and the therapeutic effect of sdr5-fc in the high-dose group is higher than that in the low-dose group.