Effects of Houttuynize Herba on IκBα/NF-κB signaling pathway by regulating intestinal flora in mice with gastric ulcer
Objective To investigate the effects of Houttuynize Herba decoction on aspirin-induced gastric ulcer(GU)in mice;To discuss its mechanism.Methods A total of 64 SPF male mice were selected,and 48 mice were randomly selected to establish the model by gavage of 20 mg/ml aspirin solution.The remaining 16 rats were treated as normal group by gavage with the same amount of normalsaline once a day for 7 consecutive days.After successful modeling,the remaining mice in the model group were randomly divided into 5 groups,with 8 mice in each group,namely normal saline group(given normal saline),omeprazole group(given omeprazole 0.5 mg/ml),Houttuynize Herba high-,medium-and low-dosage groups(given 1.08 g/ml,0.54 g/ml,0.27 g/ml),and the remaining 8 mice in the normal group were given the same amount of normal saline by gavage.The mice were treated by gavage once a day for 7 days.The number of Escherichia coli and Bifidobacterium in mouse feces was counted by bacterial culture method,and the ratio of Bifidobacterium to Escherichia coli(B/E value)was used to judge the imbalance of bacterial flora.The expression of interleukin-6(IL-6)in serum was detected by magnetic particle chemiluminescence.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression of prostaglandin E2(PGE2)in the serum of mice to determine the level of inflammation.Hematoxylin-eosin staining was used to determine the ulcer and healing.ImageJ 1.8.0 was used to calculate the ulcer inhibition rate.The protein expression levels of IκBα,NF-κB-p65 subunit and phosphorylated IκBα(p-IκBα)and p65(p-NF-κB-p65)subunits in gastric tissue of mice were evaluated by Western blot.Results Compared with the normal group,the epithelial cells of the gastric mucosa were missing,the glands were irregularly arranged,and the tissue structure was severely damaged in the modeling group;the number of Escherichia coli in the intestine increased(P＜0.01),the number of Bifidobacterium decreased(P＜0.01),and the B/E value was less than 1(P＜0.01);Serum PGE2 levels were decreased(P＜0.01),IL-6 levels were increased(P＜0.01);The expression of p-IκBα and p-NF-κB-p65 proteins in gastric tissues was elevated(P＜0.05).After 7 days of drug treatment,compared with the saline group,gastric mucosal cells and structures were improved,and weight gained in the Houttuynize Herba groups(P＜0.05);the rate of inhibition of ulcers in mice in the Houttuynize Herba high-dosage group was significantly improved(P＜0.01);the number of Bifidobacteria in the intestinal tract significantly increased(P＜0.01),that of Escherichia coli was diminished(P＜0.05),B/E value was greater than 1(P＜0.05),IL-6 content in peripheral blood was reduced(P＜0.05),PGE2 levels significantly increased(P＜0.01);the level of p-IκBα/IκBαand p-NF-κB-p65/NF-κB-p65 in the gastric tissues of mice decreased(P＜0.01).Conclusion Houttuynize Herba decoction can effectively improve gastric mucosal injury in mice,and its mechanism may be related to regulating intestinal microorganisms,inhibiting the opening of IκBα/NF-κB pathway,and reducing inflammatory response.
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