Saikosaponin regulates HIF-1α/BNIP3 signaling pathway to inhibit mitochondrial autophagy for the treatment of functional dyspepsia in rats with liver-gastric disharmony
- VernacularTitle:柴胡皂苷调节HIF-1α/BNIP3信号通路抑制线粒体自噬治疗肝胃不和型功能性消化不良大鼠
- Author:
Zheng-Liang QI
1
;
Xiao LIU
;
Man TIAN
Author Information
- Keywords: Functional dyspepsia of liver stomach disharmony type; Mitochondrial autophagy; Saikosapo-nin; HIF-1α/BNIP3 signaling pathway; rats; gastric antrum tissue
- From: Chinese Pharmacological Bulletin 2024;40(12):2256-2261
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the effect of saikosapo-nin on mitochondrial autophagy in rats with functional dyspepsia(FD)of liver stomach disharmony type by regulating the hypoxia inducible factor-1α(HIF-1α)/BCL2/adenovirus E1B interacting protein 3(BNIP3)signaling pathway.Methods A compound factor method was used to construct a liver stomach disharmo-ny type FD rat model.The rats were randomly separa-ted into a blank group,a model group,a dompendone group,and low,medium,and high dose saikosaponin groups,with 10 rats in each group.The gastrointesti-nal function of rats in each group was observed,inclu-ding gastric emptying rate and small intestine propul-sion rate,ELISA method was applied to detect serum levels of motilin(MTL)and gastrin(GAS),his-topathologic changes of the gastric sinus were observed by HE staining,transmission electron microscopy was applied to observe the mitochondrial structure of gastric antrum tissue,reagent kit was applied to detect levels of ROS,MDA,and SOD,Western blot was applied to detect the expression of mitochondrial LC3,Beclin1,p62,HIF-1α,and BNIP3 proteins in gastric antrum tissue.Results Compared with the blank group,the gastric antrum tissue of rats in the model group showed a small amount of inflammatory cell infiltration,mito-chondrial swelling and deformation,and a large num-ber of autophagosomes,the gastric emptying rate,small intestine propulsion rate,MTL,GAS,SOD,and p62 were greatly reduced,the levels of ROS,MDA,the protein expression of LC3 Ⅱ/LC3 I,Beclin1,HIF-1α,and BNIP3 were greatly increased(P＜0.05);compared with the model group,the symptoms of gastric antrum tissue were greatly improved in the dompendone group,low,medium,and high-dose sai-kosaponin groups,with clear mitochondrial cristae and reduced autophagosomes,the gastric emptying rate,small intestine propulsion rate,MTL,GAS,SOD,and p62 were greatly increased,the levels of ROS,MDA,the protein expression of LC3 Ⅱ/LC3 Ⅰ,Beclin1,HIF-1α,and BNIP3 were greatly reduced(P＜0.05).Conclusion Saikosaponin can improve gas-trointestinal function and inhibit mitochondrial autoph-agy in liver stomach disharmony type FD rats,and its mechanism of action may be related to the inhibition of the HIF-1α/BNIP3 signaling pathway.
