Role of junctional adhesion molecule C in the pathogenesis of hyperlipidemic acute pancreatitis and the effect of Shanzhachengqi Decoction on its expression

Abstract

Objective To investigate the therapeutic efficacy of Shanzhadachengqi Decoction on the capillary endothelial cell barrier dysfunction of the intestinal tract in hyperlipidemic acute necrotizing pancreatitis (HANP) rats,and to explore the possible molecular mechanism.Methods Male Sprague-Dawley rats (n =120) were randomly divided into hyperlipidemic (HL) group,HANP group,simvastatin group and Shanzhadachengqi Decoction(SD) group.The hyperlipidemic model was established by 4 weeks fat-rich food and Triton WR1339 intravenous injection.The rats in the latter 3 groups underwent intraperitoneal injection of cerulein and lipopolysaccharid to induce the acute necrotizing pancreatitis (ANP) (HANP model).The rats in simvastatin group received simvastatin gastric lavage (2.6 mg/kg) 2 h before HANP model induction,2,4,12 h after HANP model induction,while the rats in SD group received Shanzhadachengqi Decoction gastric lavage (2 ml) at the same time points,then the rats were sacrificed at 6,12,and 24 h after model induction.One hour before the rats were sacrificed,they were injected with 2％ Evens Blue.Levels of serum amylases,triacylglycerol (TG),free fatty acid (FFA) and junctional adhesion molecule C (JAM-C) were examined; the pathological changes and ultramicrostructure in intestine tissues were observed; expression of JAM-C mRNA and capillary permeability in intestine tissues were determined.Results The serum levels of JAM-C,TG,FFA in HANP group was not significantly different from those in the HL group,but the serum level of amylase was significantly increased [(4 963 ± 531) vs (885 ± 28) U/L,P =0.003].The pathology change and the ultramicrostructure showed histopathological changes in intestine tissues in HANP group were more severe,and the intestine tissular capillary permeability [(201.83 ± 8.50) vs (54.23 ± 5.79) μg/ml,P =0.000],the expression of JAM-C mRNA [(4.46 ±0.16) vs (2.08 ±0.35),P=0.002)] was significantly higher than those in the HL group,and the difference between the two groups was statistically significant (P ＜ 0.05).Compared with HANP group,the serum level of amylases [(991 ±61) vs (4 963 ±531)U/L,P=0.003],TG [(20.68 ± 2.68) vs (95.73 ± 2.190 mmol/L,P =0.000],FFA [(1 238 ± 37) vs (3 879 ± 64) μmol/ L,P=0.000],JAM-C [(166.44± 10.26) vs (396.99± 12.15) ng/L,P=0.000] in SD group were significantly decreased.Pathology change and the ultramicrostructure showed histopathological changes in intestine tissues were attenuated.The intestine tissular capillary permeability [(39.90 ± 3.62) vs (201.83 ± 8.50) μg/ml,P =0.000],the expression of JAM-C mRNA [(1.38 ± 0.10) vs (4.46 ± 0.16),P =0.003] were significantly decreased,and the difference between the two groups was statistically significant (P ＜ 0.05).The decreased degree of corresponding values in simvastatin group wsa lower than those in SD group.Conclusions Shanzhadachengqi Decoction can improve the course of HANP rat; and relieve the intestine tissuior capillary leakage,which may be related with the down-regulation of JAM-C expression in intestine tissues. Key words: Pancreatitis, aucte necrotizing; Hyperlipidemias; Gapillary permeability; Junctional adhesion molecule C; Shanzhadachengqi decoction