Effect Of Poly(ADP-ribose) Polymerase On The Injury Of Intestinal Mucosal Barrier In Rat Model With Severe Acute Pancreatitis Through NF-?B Pathway

Background Severe acute pancreatitis(SAP)is one of the most common diseases in the department of Intensive Care Unit.It is the most severe type of pancreatitis.It has the characteristics of rapid onset,rapid progress and high mortality.Systemic inflammatory response,leading to multiple organ failure,especially intestinal mucosal barrier damage occurs in the late stages of severe acute pancreatitis,which can cause bacterial flora to shift and migrate into the blood circulation,resulting in bacteremia and further exacerbation Multiple Organ Dysfunction Syndrome(MODS)and ultimately death.Poly(ADP-ribose)polymerase-1(PARP-1)is a nuclear DNA binding protein that plays an important role in DNA repair,chromatin structure,necrosis,inflammation and other functions.Recent studies have shown that it also plays an important role in the immune response and can regulate NF-?B and its downstream cells including IL-6 and TNF-a,thereby participating in the inflammatory response,but its role in the intestinal mucosal barrier damage in severe acute pancreatitis remains to be studied.Objective To investigate the effects of poly(ADP-ribose)polymerase-1(PARP-1)inhibitors in intestinal mucosal barrier injury in a rat model with severe acute pancreatitis(SAP).Method Twenty healthy male Wistar rats were divided into four groups(n=5/group)using a random table method—control,SAP,3-aminobenzamide(3-AB),and 3-AB control groups.The SAP model was induced by intraperitoneal injection of cerulean(6 times)with lipopolysaccharide(1 time).At 30 minutes,the rats were treated with the PARP inhibitor,3-AB,or normal saline.After 12 hours,all rats were killed to harvest pancreas tissues,intestines tissues,and blood from the hearts for index detection.Serum amylase(AMY)and interleukin-6(IL-6)levels were measured using an automatic biochemical instrument and enzyme-linked immunosorbent assay(ELISA),respectively.The protein expression of PARP-1 and nuclear factor(NF-?B)were measured using western blot and that of Occludin was measured using an immunohistochemical test.The measurement data were expressed as mean ± standard deviation(Mean ± SD).One-way analysis of variance was used for comparison of multiple groups of variables.Non-parametric tests of rank conversion were used when variances were not uniform.P <0.05 was considered statistically significant.Results Compared to the control group,the following in the SAP group were significantly increased: ascites(with serious hemorrhage and necrosis in the pancreas and disordered intestinal villi),serum AMY and IL-6 levels,and the expression of PARP-1 and NF-?B.However,expression of Occludin protein was significantly decreased.There was no significant difference between 3-AB group and 3-AB control group.Compared to the SAP group,the severity of SAP and pancreatitis-associated intestinal injury was significantly attenuated with the administration of 3-AB.Serum AMY and IL-6 levels were significantly decreased(serum AMY,1879.25 ± 736.6 vs.5569.33 ± 1993.48 U/L;IL-6,77.98 ± 20.65 vs.209.14 ± 79.08 pg/m L,both P<0.05),but the expression of PARP-1 and NF-?B were significantly increased(PARP-1,1.44 ± 0.09 vs.1.49 ± 0.13;NF-?B,0.63 ± 0.09 vs.0.96 ± 0.08).Similarly,the expression of Occludin was significantly decreased(6.7 ± 1.5 vs.3.2 ± 1.1,P<0.05).Conclusion Inhibition of PARP-1 expression has protective effects on SAP intestinal mucosal barrier damage.The mechanism may be related to the inhibition of NF-?B signaling pathway and increase intestinal mucosal Occludin protein expression.