养阴活胃方调控NQO1/P53/GPX4轴改善慢性萎缩性胃炎鼠胃粘膜损伤的作用机制OA

Objective To investigate the mechanism by which Yangyin Huowei Formula(养阴活胃方,YYHWF)ameliorates gastric mucosal injury(GMI)in a rat model of chronic atrophic gastritis(CAG)through regulating the NQO1/P53/GPX4 axis.Methods The CAG rat model was established using N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)combined with irregular feeding.Specific pathogen-free(SPF)male Sprague-Dawley(SD)rats were randomly divided into the following groups:blank control,model,low/medium/high-dose YYHWF,vitacoenzyme(positive control),and dicoumarol/β-lapachone intervention groups.Treatments were administered continuously for 8 weeks.Gastric mucosal pathological changes were assessed by hematoxylin-eosin(HE)staining.The mRNA and protein expression levels of NAD(P)H quinone dehydrogenase 1(NQO1),tumor protein p53(P53),solute carrier family 7 member 11(SLC7A11),and glutathione peroxidase 4(GPX4)were detected by reverse transcription-quantitative polymerase chain reaction(RT-qPCR)and Western blot(WB),respectively.Results Compared with the blank control group,the model group exhibited significant gastric mucosal glandular atrophy,inflammatory infiltration,upregulated expression of NQO1 and P53,and downregulated expression of SLC7A11 and GPX4(all P<0.001).The high-dose YYHWF group markedly improved gastric mucosal histopathology(reduced glandular atrophy and inflammatory infiltration),downregulated NQO1 and P53 expression,and upregulated SLC7A11 and GPX4 expression in a dose-dependent manner(all P<0.01).Following dicoumarol(an NQO1 inhibitor)intervention,the high-dose YYHWF combined with dicoumarol group showed further reductions in NQO1 and P53 expression alongside increased SLC7A11 expres-sion(all P<0.01).Conversely,β-lapachone(an NQO1 activator)intervention reversed the protective effects of YYHWF,upregulating P53 and suppressing SLC7A11 and GPX4 expression(all P<0.01).Conclusion YYHWF ameliorates gastric mucosal lesions in CAG model rats by suppressing ferroptosis,likely through inhibiting the NQO1/P53 pathway and activating the SLC7A11/GPX4 pathway.This molecular mechanism aligns with the TCM principle of"nourishing yin,resolving stasis,and harmonizing yin and yang"providing a scientific basis for the integrated use of Chinese and Western medicine in CAG management.