Mechanism of the nuclear factor kappa B in intestinal mucosal barrier damage in rats with severe acute pancreatitis

Abstract

Objective To investigate the role of the nuclear factor-kappa B (NF-κB) in intestinal mucosal barrier injury in rats with severe acute pancreatitis (SAP). Methods A total of 24 Wastar rats were divided into the control group, the SAP group and the NF-κB inhibitor group [i.e. the pyrrolidine dithiocarbamate (PDTC) group] according to the random number table method, 8 rats in each group. The SAP rat models were made, rats in the control group were only turned the pancreas, and rats in the PDTC group were injected with 40 mL/kg PDTC solution through tail veins after modeling for 2 h. Rats in each group were sacrificed after modeling for 24 h. Then the gross changes in the abdominal cavity of rats in each group were observed; the pathological changes of the intestinal mucosa, the change of permeability, and the expressions of tumor necrosis factor-alpha (TNF-α) and interleukin 1 (IL-1) were compared. The expression of Occludin in intestinal mucosal epithelial cells of rats was detected by the immunohistochemical method. Results There was no obvious inflammation in the abdominal cavity and no edema and hyperemia in the intestinal tract of rats in the control group, while the rats in SAP and PDTC groups had different degrees of ascites, intestinal edema and hyperemia, and rats in the SAP group were more serious. No obvious damage can be seen in the intestinal mucosa in the control group under the optical microscope, while different degrees of intestinal mucosal damage were observed in the ileum of rats in the SAP and PDTC groups, and the PDTC group was lighter. The pathological scores [(3.6 ± 1.4), (21.3 ± 3.7), (33.8 ± 4.2)] and the intestinal mucosal permeability [(22 ± 6), (188 ± 26), (328 ± 35) nL·min-1·cm-1] were significantly different in these three groups (F = 7.259, 6.402; both P < 0.05). The permeability of intestinal mucosa in the SAP group increased more markedly as compared to the PDTC group (P < 0.05). The expressions of TNF-α [(146 + 37), (1 684 + 80), (2 896 + 99) ng/L] and IL-1 [(53 ± 10), (1 756 ± 60), (2 893± 88) ng/L] in these three groups both showed statistical significance (F = 5.751, 7.247; both P < 0.05). The expressions of TNF-α and IL-1 in the intestinal tract in SAP and PDTC groups were significantly higher than those in the control group (all P < 0.05), and the expressions of TNF-α and IL-1 were higher in the SAP group than in the PDTC group (all P < 0.05). The immunohistochemical results showed that the Occludin proteins in the control group were distributed along the epithelial cells of the intestinal mucosa and showed a strong brown linear signal. The localization of Occludin in the PDTC group was not significantly different from that in the control group, but the positive brown signal was weakened, and the positive cells decreased significantly in the SAP group. There was significant difference of Occludin expressions [(15.6 ± 3.0), (6.4 ± 1.4), (3.1 ± 1.2)] in these three groups (F = 5.427, P < 0.05). Conclusion The intestinal mucosal barrier damage in SAP rats may be related to the increase of the NF-κB expression in intestinal tissues, thus down-regulation of the Occludin expression in intestinal epithelial cells and the inhibition of the NF-κB expression would have a protective effect on the intestinal mucosal barrier of SAP. Key words: Severe acute pancreatitis; Intestinal mucosal barrier; Nuclear factor-kappa B; Inflammatory factor