温中益气方调控TLR4-NF-κΒ通路对胃溃疡的抗炎机制研究OA

Objective:To explore the therapeutic effect and mechanism of Wenzhong Yiqi decoction on gastric ulcer in rats by acetic acid burning method.Methods:Sixty SD rats were randomly divided into sham operation,mod-el,omeprazole,and low-,medium-,and high-dose treatment groups,with 10 rats in each group.Except the sham op-eration group,the other groups were used acetic acid burning method to establish gastric ulcer model.The rats in each group were given intragastric administration of Wenzhong Yiqi decoction once a day.The low-,medium-,and high-dose group was given 0.6,1.2 and 2.4 g/kg.The rats in omeprazole positive group were given the contents of omeprazole enteric-coated capsules at a dose of 0.36 g/kg,and the rats in sham operation group were given the same volume of 0.9%sodium chloride solution by gavage.The rats in each group were treated by intragastric administra-tion for 14 days.After the last administration,the relevant parameters were measured,including gastric acid pH;ser-um levels of superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-PX),nitric oxide(NO),inducible nitric oxide synthase(i-NOS)and total nitric oxide synthase(t-NOS)were measured.The ulcer ar-ea and ulcer inhibition rate were measured.Hematoxylin-eosin staining(HE)was used to observe the pathological changes of gastric ulcer tissue in each group.The protein levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in gastric tissue were detected by enzyme-linked immunosorbent assay(ELISA).RT-qPCR was used to detect the mRNA expression in ulcer tissue.Western blotting was used to detect the expression of related proteins.Results:Compared with the sham-operation group,the pH value of gastric acid in the model group tended to decrease.Com-pared with the model group,the pH value of gastric acid in the low dose of group did not change significantly,while the pH value of gastric acid in the medium and high dose groups increased significantly(P<0.05)and the ulcer area of Wenzhong Yiqi decoction treatment groups was significantly reduced(P<0.05).Compared with the sham opera-tion group,the levels of NO,SOD and GSH-PX in the serum of the model group were significantly decreased(P<0.01),and the levels of t-NOS and MDA were significantly increased(P<0.01).Compared with the model group,the serum levels of NO,t-NOS,SOD and GSH-PX in each administration group were significantly increased(P<0.05).The levels of i-NOS and MDA were significantly decreased(P<0.05).Pathological observation showed that after the treatment with Wenzhong Yiqi decoction,the morphological structure of gastric mucosa around the ulcer in the high-dose group tended to be further normal,and a little new granulation tissue was observed in the injured site.Compared with the sham operation group,the TNF-αand IL-6 protein levels in the gastric tissue of the model group were significantly increased(P<0.05).The contents of TNF-αand IL-6 protein in gastric tissue of rats in each ad-ministration group were significantly decreased(P<0.05).Compared with the sham operation group,the expression levels of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88)and nuclear factor kappa B(NF-κB)p65 mRNA in the model group were significantly increased(P<0.05).Compared with the model group,the expres-sion levels of TLR4,MyD88 and NF-κΒ p65 mRNA in the gastric ulcer tissue of the rats in each treatment group were significantly decreased(P<0.05),and the protein expression levels of TLR4,MyD88 and NF-κΒp65 in the gastric ulcer tissues of the drug groups were significantly decreased(P<0.05).Conclusion:Wenzhong Yiqi decoction has a strong therapeutic effect on gastric ulcer in rats and can promote the healing of gastric ulcer possibly by inhibi-ting the TLR4-NF-κΒ signaling pathway and promoting the regeneration of gastric mucosa by inhibiting oxidative stress and inflammatory stimulation.