The mechanism of poly (ADP-ribose) polymerase on the intestinal mucosal barrier injury in rat model with severe acute pancreatitis through NF-κB signaling pathway / 中华急诊医学杂志

ABSTRACT

Objective:To investigate the effects of poly (ADP-ribose) polymerase-1(PARP-1) in intestinal mucosal barrier injury in rat model with severe acute pancreatitis (SAP).Methods:Twenty healthy male Wistar rats were divided into four groups ( n=5 each 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 with lipopolysaccharide. At 30 min, the rats were treated with the PARP-1 inhibitor, 3-AB, or normal saline,separately. After 12 h, all rats were sacrificed to harvest pancreas tissues, intestines tissues, and blood from the hearts for index detection. Serum amylase (AMY) and interleukin (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-κB) were measured using Western blot and that of occludin was measured using an immunohistochemical test. 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. A P <0.05 was considered statistically significant. Results:Compared to the control group, the following indexes 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-κB. However, Occludin expression 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 1 879.25 ± 736.6 U/L vs 5 569.33 ± 1993.48 U/L; IL-6 77.98 ± 20.65 pg/mL vs 209.14 ± 79.08 pg/mL, both P<0.05), but the expression of PARP-1 and NF-κB were significantly increased (PARP-1 1.44 ± 0.09 vs 1.49 ± 0.13; NF-κB 0.63 ± 0.09 vs 0.96±0.08, both P<0.05). Similarly, Occludin expression was significantly decreased (6.7±1.5 vs 3.2±1.1, P<0.05). Conclusions:Inhibition of PARP-1 has protective effects on SAP associated intestinal mucosal barrier damage. The mechanism may be related to the inhibition of NF-κB signaling pathway and increase intestinal mucosal Occludin protein expression.