Effects of Matrine on Inflammatory Response and Ulcer Repair in Rats with Gastric Ulcer through HMGB1/TLR4/NF-κB Pathway
Objective:To investigate the effects of matrine on the inflammatory response and ulcer repair in gastric ulcer(GU)rats as well as its regulatory role on the high mobility group box 1(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor-KB(NF-κB)signaling pathway.Methods:Male SD rats were randomly divided into a normal control group,a model control group,matrine 0.1 g/kg and 0.2 g/kg groups,gly-cyrrhizic acid(HMGB1 inhibitor)0.03 g/kg group,and matrine 0.2 g/kg+glycyrrhizic acid 0.03 g/kg group,with 12 rats in each group.The GU model was induced in rats except for those in the normal control group by the acetic acid burning method.After successful modeling,intragastric administration was performed once a day for 28 days.General behavioral changes in rats were observed.Ulcer index and ulcer in-hibition rate of rats were detected.The morphological changes in rat gastric mucosal tissue were observed by transmission electron morpholo-gy.TUNEL assay was used to detect the apoptosis rate of gastric mucosal epithelial cells.The positive expression level of TLR4 in gastric mu-cosal tissue was detected by immunofluorescence.The positive expression levels of HMGB1 and NF-κB in gastric mucosal tissue were detec-ted by immunohistochemistry.Western blot was used to detect the protein expression of interleukin-6(IL-6),cyclooxygenase-2(COX-2),myeloid differentiation factor 88(MyD88),DNA damage marker protein phosphorylated histone H2AX(γH2AX),repair-related protein CtIP,and Rad51.Results:Compared with the normal control group,rats in the model control group exhibited hunching,pus and blood in fe-ces,gastric mucosal bleeding,severe damage to gastric mucosal epithelial cell structure,up-regulated ulcer index,gastric mucosal epithelial cell apoptosis rate,protein expression of TLR4,HMGB1,NF-κB,IL-6,COX-2,MyD88,and γH2AX,and downregulated protein expression of CtIP and Rad51(P＜0.01).Compared with the model control group,rats in the matrine 0.1 g/kg and 0.2 g/kg groups and the glycyrrhizic acid 0.03 g/kg group showed alleviation of fecal blood and gastric mucosal epithelial cell structure damage,decreased ulcer index and gastric mucosal epithelial cell apoptosis rate,downregulated protein expression levels of TLR4,HMGB1,NF-κB,IL-6,COX-2,MyD88,and γH2AX,increased ulcer inhibition rate,and upregulated protein expression of CtIP and Rad51(P＜0.01).The improvement in the above symptoms and indicators in the matrine 0.2 g/kg+glycyrrhizic acid 0.03 g/kg group was significantly better than that in the matrine 0.2 g/kg group(P＜0.01).Conclusion:Matrine may inhibit the activation of the HMGB1/TLR4/NF-κB pathway,thereby suppressing inflammatory response and apoptosis of gastric mucosal epithelial cells,promoting ulcer repair,and improving gastric mucosal tissue damage in GU rats.
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