Efficacy Of Resolvin D1 On The Prevention Of Acute Pancreatitis In Mice And Its Mechanism

Background Resolvin D1 is a kind of pro-resolving mediators derived from polyunsaturated fatty acids, according to the synthesis of precursors, in different ways, can be divided into Resolvin D, Resolvin E and aspirin triggered resolvin(AT-Rv D). The study found that Resolvin with potent anti-inflammatory in a variety of inflammatory disorders. AT-Rv D1 showed a higher potency in preventing dextran sulfate sodium-induced colitis, and reduced the levels of TNF-α, IL-1β, MIP-2. Zhao XW study found that diclofenac can reduce the incidence of PEP, the level of Rv D1 in the diclofenac group at 3h and 24 h after ERCP were significantly increased compared with the control group, it is suggested that diclofenac reduce the incidence of PEP by increase the level of Rv D1.Objective To investigate the protective effects of Resolvin D1 on acute pancreatitis in mice and its mechanism.Methods 24 male C57BL/6 mice were randomly divided into control group, AP group and Rv D1 group. AP was induced by peritoneal injections of caerulein(50ug·kg-1) at hourly intervals for 7 times. Rv D1(50ug·kg-1) was administered to mice by peritoneal injection at one hours before the first injection of caerulein, the control group was given normal saline. The serum amylase and lipase was analysis biochemically and the level of IL-1?、IL-6、IL-8、TNF-ɑ in the serum and the pancrea and lung was detected by ELISA method. the MPO activity in the pancrea and lung were detected and thepathological changes of pancreas and lung were observed.Results The serum amylase 、 lipase and pancreatic wet/weight in the AP group( 165.71±18.78U/dl、1240.69±536.13U/L、0.0055±0.0012, respectively), were significantly increased compared with control group(149.91±1.40U/dl 、328.03±204.14U/L、0.0033±0.0017), P<0.05. The pathological changes of pancreas reveal interstitial hyperemia and edema, a large number of inflammatory cell infiltration and acinar swelling. Meanwhile, the MPO activity and the levels of IL-1?、IL-6、IL-8、TNF-ɑ in AP group were significantly increased compared with control group(P<0.05). The serum amylase、lipase and pancreatic wet/ weight in the Rv D1 group(144.79±11.63 U/dl、730.05±183.84 U/L、0.0043±0.0007, respectively), were significantly decreased compared with AP group(165.71±18.78U/dl、1240.69±536.13 U/L、0.0055±0.0012), P<0.05. And the MPO activity and the levels of IL-1?、IL-6、IL-8、TNF-ɑ in Rv D1 group were significantly decreased(P<0.05).Conclusion Rv Dl can inhibit the production of inflammatory mediator and alleviate the pancreatitis in mice.Backgroud ERCP is an important means of diagnosis and management of biliary and pancreatic diseases. The complications of ERCP include hemorrhage, perforation, infection, and the PEP is the most common complication of ERCP. There is no curative effect affirmation drug for the prevention of PEP, numerous study results were not satisfactory. Recently, study found that NSAIDs can prevent the PEP, but the exact mechanisms are not fully clarified. So, we explore the efficacy and mechanism of diclofenac in the prevention of post–ERCP pancreatitis.Objective To investigate the efficacy and mechanism of diclofenac in the prevention of post–ERCP pancreatitis.Methods A total of 120 patients with choledocholithiasis were collected from September 2012 to October 2013 and were randomly divided into diclofenac group(n=60) and control group(n=60). The diclofenac group patients to receive a single dose of intramuscular diclofenac immediately after ERCP. Serum amylase level was measured before and 3h and 24 h after ERCP, and the rate of acute pancreatitis after ERCP were assessed. The Lipoxin A4、Resolvin D1 and Resolvin E1 levels were measured before and 3h and 24 h after ERCP in 30 patients from diclofenac group and 30 patients from control group.Results Patients developed PEP in diclofenac group was 6.67%, and significantlydecreased compared with control group(20.00%, P <0.05). Serum amylase levels at 3h after ERCP in diclofenac and control groups were(214.93±309.28)U/L and(328.70±369.55)U/L, respectively(P>0.05), which were(192.50±282.37)U/L and(251.17±175.18)U/L, respectively, at 24 h after ERCP(P>0.05). The Lipoxin A4 levels in diclofenac group at 3h and 24 h after ERCP were 401.69±89.08ng/ml 、423.99±96.61ng/ml, which were significantly increased compared with the control group 357.04±70.70ng/ml 、 372.12±91.26ng/ml, respectively( P= 0.036,P=0.037); The Resolvin D1 levels in diclofenac group at 3h and 24 h after ERCP were 447.12±91.75pg/ml、414.49±68.78pg/ml, which were significantly increased compared with the control group 387.98±86.39pg/ml 、 351.09±112.72pg/ml, respectively(P=0.013,P=0.011); The Resolvin E1 levels in diclofenac group at 3h and 24 h after ERCP were 590.69±79.64 pg/ml 、 587.44±65.96 pg/ml, which were significantly increased compared with the control group 531.40±56.24 pg/ml、546.79±74.78 pg/ml, respectively(P=0.002,P=0.029); The Lipoxin A4、Resolvin D1 and Resolvin E1 levels in diclofenac group at 3h were 401.69±89.08 ng/ml、447.12±91.75 pg/ml、590.69±79.64 pg/ml, which were significantly increased compared with the before ERCP 304.96±70.46 ng/ml、403.26±54.33 pg/ml、542.84±75.16 pg/ml, respectively(P<0.05).Conclusion Diclofenac given immediately after ERCP can reduce the incidence of PEP. The anti-pancreatitis mechanism of diclofenac may be associated with the increasement of the levels of Lipoxin A4、Resolvin D1 and Resolvin E1.