Effect and mechanism of epigallocatechin gallate on intestinal injury in sepsis
Objective:To investigate the effect and mechanism of epigallocatechin gallate(EGCG)on intestinal injury in sep-sis rats.Methods:32 Male SD rats were randomly divided into Sham group(Sham group),sepsis group(CLP group),sepsis+EGCG group(EGCG group)and sepsis+GSK2606414 intervention group(GSK group),with 8 rats in each group.In Sham group,only the cecum was observed and the abdomen was closed immediately after laparotomy.Caecal ligation and perforation were performed in CLP group.EGCG group was intraperitoneally injected 50 mg/kg of EGCG after CLP.The GSK group was given 100 mg/kg of GSK2606414 per day for one week before CLP.The 4 groups of rats were killed 24 h after the modeling,and serum and intestinal tissue samples were collected and preserved.The pathological changes of intestinal tract in rats were observed by hematoxylin-eosin staining.enzyme-linked immunosorbent assays was used to detect the levels of IL-1β and IL-6 in serum of rats.The positive area percentage of phosphorylated protein kinase R-like endoplasmic reticulum kinase(p-PERK),CCAAT en-hancer binding protein homologous protein(CHOP),aspartate-specific cysteine proteinase-12(Caspase-12)and Claudin-1(Clau-din-1)in intestinal tissue was observed by immunohistochemistry.The expressions of p-PERK,R-like endoplasmic reticulum ki-nase(PERK),CHOP,Caspase-12 and Claudin-1 in rat intestinal tissues were detected by Western blotting.Results:The intesti-nal villi structure of CLP group was seriously damaged,and a large number of inflammatory cells could be seen under the micro-scope.The pathological injury of EGCG and GSK groups was less than that of CLP group,and the Chiu's score of CLP group was significantly higher than that of EGCG and GSK group(P<0.05).Serum levels of IL-1β and IL-6 in CLP group were significant-ly higher than those in Sham group,and serum levels of inflammatory factors in EGCG group and GSK group were significantly lower than those in CLP group(P<0.05).The percentage of positive area of P-PERK,CHOP and Caspase-12 in the intestinal tissue of rats in CLP group was significantly higher than that in Sham group,while the percentage of positive area in EGCG group and GSK group was significantly lower than that in CLP group(P<0.05).The percentage of Claudin-1 positive area in intestinal tissue of rats in CLP group was significantly lower than that in Sham group,and the percentage of positive area in intestinal tissue of rats in EGCG group and GSK group was significantly higher than that in CLP group(P<0.05).The expression levels of P-PERK,CHOP and Caspase-12 in the intestinal tissues of rats in CLP group were higher than those in Sham group,and the above levels in EGCG and GSK groups were lower than those in CLP group(P<0.05).The expression level of Claudin-1 protein in the intestinal tissues of CLP group was lower than that of Sham group,and the above indexes in EGCG and GSK groups were higher than those in CLP group(P<0.05).Conclusion:Epigallocatechin gallate has certain therapeutic effect on intestinal injury in sep-sis,and its mechanism may be related to the inhibition of endoplasmic reticulum stress(ERS)apoptotic pathway.
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