Mechanism of electroacupuncture-mediated PINK1/Parkin signal pathway in the treatment of functional dyspepsia in rats

HE Yuhan ,  

SONG Yuhui ,  

QIU Yi ,  

HUANG Yuhan ,  

ZHU Mohao ,  

KANG Zhen ,  

LIU Wei′ai ,  

摘要

ObjectiveTo investigate the mechanism of electroacupuncture-mediated PTEN-induced kinase 1(PINK 1)/Parkin signal pathway activation in treating functional dyspepsia model rats.MethodsThirty-six SD rats were randomly divided into the blank control (n=8) and the modeling groups (n=28) using the random number table method. The functional dyspepsia model was established using the compound etiology modeling method. After successful modeling, 24 rats were divided into the model, electroacupuncture, and mosapride groups using the random number table method, with eight rats per group. The blank group was not intervened. The electroacupuncture, mosapride, and model groups were bound for 30 min, and only the electroacupuncture group was administered " Neiguan" (PC 6) and " Gongsun" (SP 4) while bound. The electroacupuncture and model groups were administered the same amount of normal saline, and the mosapride group was given mosapride citrate solution (1.35 mg/kg). The above intervention method were performed once a day for 7 consecutive days to observe the general condition of rats. Gastric emptying and small intestinal propulsion experiments were used to observe gastric emptying rate and small intestine propulsion rate in each group of rats. The interstitial cells of the Cajal (ICC) ultrastructure of gastric antrum were observed under a transmission electron microscope. The protein and mRNA expressions of C-kit proto-oncogene protein (C-kit), microtubule-associated protein 1 light chain 3 (LC3) Ⅱ/Ⅰ, ubiquitin-binding protein p62 (p62), Bcl-2 interacting protein 1 (Beclin1), PINK1, and Parkin were detected using Western blotting and real-time fluorescence PCR.ResultsCompared with the blank group, the rats in the model group exhibited lethargy, dull and dry fur, sluggish responses, and substantial decreases in food intake and body weight. Their feces alternated between dry and loose consistency. Furthermore, the gastric emptying and small intestinal propulsion rates were reduced(P<0.01). The ultrastructural morphology of ICC and their mitochondria in the gastric antrum tissue showed apparent damage. The protein and mRNA expressions of C-kit and p62 were decreased (P<0.01), whereas those of PINK1, Parkin, Beclin1, and LC3Ⅱ/Ⅰ were increased (P<0.01). Compared with the model group, the rats in the electroacupuncture and mosapride groups showed notable improvements in their mental state, with neat fur, enhanced activity and responsiveness, gradual increases in food intake and body weight, and well-formed feces. Additionally, the gastric emptying and intestinal propulsion rates increased(P<0.01). The ultrastructural morphology of ICC and their mitochondria in the gastric antrum tissue were notably improved. The protein and mRNA expressions of C-kit and p62 were increased (P<0.01), whereas those of PINK1, Parkin, Beclin1, and LC3Ⅱ/Ⅰ were decreased (P<0.01).ConclusionElectroacupuncture improves the gastrointestinal motility of functional dyspepsia rats, and its mechanism may be related to upregulating C-kit and p62 expression, downregulating PINK1, Parkin, Beclin1, and LC3Ⅱ/Ⅰ expression, inhibiting abnormal PINK1/Parkin signal pathway activation, and blocking the excessive mitophagy of ICC.

关键词

functional dyspepsia;electroacupuncture;mitophagy;PTEN-induced kinase 1/Parkin signal pathway;rats

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