舒胃汤通过AMPK/ULK1/FUNDC1信号通路调控线粒体自噬缓解功能性消化不良OA

Objective:To observe the effect of Shuwei Decoction on mitochondrial autophagy in rats with functional dyspepsia(FD)by modulating the 5'adenosine monophosphate-activated protein kinase/ULK-51-like kinase 1/FUN14 domain-containing protein 1(AMPK/ULK1/FUNDC1)signaling pathway.Methods:Sixty SPF male SD rats were divid-ed into a blank control group,model control group,Shuwei Decoction groups at doses of 3.78 g/kg,7.56 g/kg,and 15.12 g/kg,and a Mosapride group(1.35×10-3 g/kg)using a random number table,with 10 rats in each group.Ex-cept for the blank control group,rats in the other five groups were subjected to a modified compound etiology modeling method(chronic restraint stress+alternate-day tail-clamping irritation+excessive fatigue+dietary disorders)for 21 days to establish an FD model with a syndrome of liver depression and spleen deficiency,After modeling,its success was evaluated.After successful modeling,rats were administered the respective interventions by gavage for 14 days.Changes in body weight and food intake of the rats were observed.In the open-field test,the total movement distance and frequen-cy were observed.A black semi-solid paste was administered by gavage to detect the gastric emptying rate and small in-testinal propulsion rate.HE staining was used to detect physiological and pathological conditions of the gastric antrum tis-sue of rats.Western blot was used to detect the protein expression levels of p-AMPK/AMPK,p-ULK1/ULK1,FUNDC1,and LC3II/lC3I.ATP content in the gastric antrum tissue was detected using kits.Immunofluorescence staining was used to detect the content and co-localization level of LAMP2 and TOMM20 in the gastric antrum tissue of FD rats with a syndrome of liver depression and spleen deficiency.Results:No obvious organic changes were observed in the gastric an-trum tissue of any group.Compared with the blank control group,the model control group showed significant reductions in body weight,food intake,total movement distance,rearing frequency,gastric emptying rate,and small intestinal propul-sion rate(P<0.05).The protein expression levels of p-AMPK/AMPK,p-ULK1/ULK1,FUNDC1,and LC3II/lC3I were significantly increased(P<0.05).The fluorescence intensities of TOMM20 and LAMP2,as well as their co-localization coefficient,were also markedly increased(P<0.05),while the ATP content was significantly decreased(P<0.05).Compared with the model control group,the Shuwei Decoction groups and the Mosapride group showed significant im-provements in body weight,food intake,gastric emptying rate,small intestinal propulsion rate,total movement distance,and rearing frequency(P<0.05 or P<0.01).The protein expression levels of p-AMPK/AMPK,p-ULK1/ULK1,FUNDC1,and LC3II/lC3I were significantly decreased(P<0.05 or P<0.01).The fluorescence intensities of TOMM20 and LAMP2,as well as their co-localization coefficient,were significantly decreased(P<0.05 or P<0.01),while the ATP content was significantly increased(P<0.05 or P<0.01).Conclusion:The mechanism of action of Shuwei Decoc-tion on FD rats with a syndrome of liver depression and spleen deficiency is related to the regulation of mitochondrial au-tophagy via the AMPK/ULK1/FUNDC1 signaling pathway.