Published online Mar 28, 2015. doi: 10.3748/wjg.v21.i12.3537
Peer-review started: September 1, 2014
First decision: October 14, 2014
Revised: November 6, 2014
Accepted: December 20, 2014
Article in press: December 22, 2014
Published online: March 28, 2015
AIM: To investigate the effect of Qingyi decoction on the expression of secreted phospholipase A2 (sPLA2) in intestinal barrier injury.
METHODS: Fifty healthy Sprague-Dawley rats were randomly divided into control, severe acute pancreatitis (SAP), Qingyi decoction-treated (QYT), dexamethasone-treated (DEX), and verapamil-treated (VER) groups. The SAP model was induced by retrograde infusion of 1.5% sodium deoxycholate into the biliopancreatic duct of the rats. All rats were sacrificed 24 h post-SAP induction. Arterial blood, intestine, and pancreas from each rat were harvested for investigations. The levels of serum amylase (AMY) and diamine oxidase (DAO) were determined using biochemical methods, and serum tumor necrosis factor (TNF)-α level was measured by an enzyme linked immunosorbent assay. Pathologic changes in the harvested tissues were investigated by microscopic examination of hematoxylin and eosin-stained tissue sections. The expressions of sPLA2 at mRNA and protein levels were detected by reverse transcriptase PCR and Western blot, respectively. A terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay was used to investigate apoptosis of epithelial cells in the intestinal tissues.
RESULTS: Compared to the control group, the expression of sPLA2 at both the mRNA and protein levels increased significantly in the SAP group (0.36 ± 0.13 vs 0.90 ± 0.38, and 0.16 ± 0.05 vs 0.64 ± 0.05, respectively; Ps < 0.01). The levels of AMY, TNF-α and DAO in serum were also significantly increased (917 ± 62 U/L vs 6870 ± 810 U/L, 59.7 ± 14.3 ng/L vs 180.5 ± 20.1 ng/L, and 10.37 ± 2.44 U/L vs 37.89 ± 5.86 U/L, respectively; Ps < 0.01). The apoptosis index of intestinal epithelial cells also differed significantly between the SAP and control rats (0.05 ± 0.02 vs 0.26 ± 0.06; P < 0.01). The serum levels of DAO and TNF-α, and the intestinal apoptosis index significantly correlated with sPLA2 expression in the intestine (r = 0.895, 0.893 and 0.926, respectively; Ps < 0.05). The levels of sPLA2, AMY, TNF-α, and DAO in the QYT, VER, and DEX groups were all decreased compared with the SAP group, but not the control group. Qingyi decoction intervention, however, gave the most therapeutic effect against intestinal barrier damage, although the onset of its therapeutic effect was slower.
CONCLUSION: Qingyi decoction ameliorates acute pancreatitis-induced intestinal barrier injury by inhibiting the overexpression of intestinal sPLA2. This mechanism may be similar to that of verapamil.
Core tip: Secreted phospholipase A2 (sPLA2) is a damage factor that stimulates excessive inflammatory responses, which can lead to the degradation and hydrolysis of biologic membranes, thus promoting epithelial injury. We demonstrate that sPLA2 is overexpressed at the mRNA and protein levels in a rat model of severe acute pancreatitis-induced intestinal barrier injury. However, a traditional Chinese medicine, Qingyi decoction, effectively antagonized this overexpression of sPLA2 to alleviate the severity of the disease. This observation was comparable to the inhibitory effect of verapamil on sPLA2 expression.