PMID- 36571220 OWN - NLM STAT- MEDLINE DCOM- 20221227 LR - 20221230 IS - 1000-0607 (Print) IS - 1000-0607 (Linking) VI - 47 IP - 12 DP - 2022 Dec 25 TI - [Electroacupuncture promotes gastrointestinal motility by activating autophagy of Cajal interstitial cells via downregulating PI3K/Akt/mTOR signaling pathway in stomach of diabetic gastro-paresis rats]. PG - 1060-7 LID - 10.13702/j.1000-0607.20211241 [doi] AB - OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Zusanli" (ST36), "Sanyinjiao" (SP6) and "Liangmen" (ST21) on gastrointestinal motility, blood glucose content and expression of autophagy-related proteins 1 light chain 3 (LC3), p62, phosphatidyli-nositol-3 kinase (PI3K), protein kinase B (Akt), p-Akt and mammalian target protein of rapamycin (mTOR) of interstitial cells of Cajal (ICCs) in the cultured gastric antrum cells in diabetic gastroparesis (DGP) rats, so as to reveal its mechanisms underlying improvement of DGP. METHODS: A total of 45 Sprague Dawley (SD) rats were randomly divided into blank control, model, EA, medication (3-methyladenine, 3-MA) and EA+3-MA groups, with 9 rats in each group. The DGP model was established by intraperitoneal injection of 2% streptozotocin (STZ) combined with high-fat and high sugar diet for 8 weeks. The gastric emptying rate was measured by using gavage of phenol red (to measure the propelling length of the phenol red/total length of small intestine x100%). The symptom score (mental state, coat color and luster, behavior and activity, stool traits) of rats was observed every week and the blood glucose content was measured by using a glucometer. EA (20 Hz/100 Hz, 2 mA) was applied to unilateral ST36, SP6 and ST21 alternatively for 15 min, once daily, 5 days a week for 3 weeks. Rats of the 3-MA and 3-MA+EA groups received intraperitoneal injection of 3-MA (30 mg.kg(-1).d(-1), 10 mg/mL), once daily, 5 days a week for 3 weeks. After 15 days' intervention, the rats were operated for gastric emptying rate test, specimen collection, isolation, and culture of primary ICCs. The expression levels of microtubule associated protein LC3, p62, PI3K, Akt, p-Akt and mTOR of ICCs of cultured gastric antrum cells were detected using Western blot, and the number of autophagosomes in ICC of gastric antrum was observed under transmission electron microscope. RESULTS: Compared with the blank control group, the symptom score, blood glucose, and the expression levels of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins were increased significantly (P<0.01), while the gastric emptying rate and ratio of LC3Ⅱ/LC3Ⅰ and the expression level of class Ⅲ PI3K protein were significantly decreased (P<0.05, P<0.01) in the model group. In comparison with the model group, the increase of symptom score, blood glucose, and expression levels of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins and the decrease of gastric empty rate and LC3Ⅱ/LC3Ⅰ ratio and the expression level of class Ⅲ PI3K protein were all reversed in both EA and EA+3-MA groups (P<0.05, P<0.01), rather than in the 3-MA group. In addition, 3-MA also reversed modeling-induced increase of class Ⅰ PI3K, Akt, p-Akt and mTOR proteins expression (P<0.01). No significant differences were found between the EA and EA+3-MA in downregulating the levels of symptom score and blood glucose content, and in upregulating gastric empty rate(P>0.05). The effect of EA was notably superior to that of EA+3-MA in upregulating the ratio of LC3Ⅱ/LC3Ⅰ and the expression level of class Ⅲ PI3K protein, and in downregulating the expression of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins (P<0.05, P<0.01). The findings of transmission electron microscopy showed obvious swelling, breakage of some mitochondrial cristae in the ICC cells of antrum and no autophagosomes in the model group and 3-MA group, which was milder in the damage of mitochondrial cristae and marked increase in the autophagosomes in both EA and EA+3-MA groups. CONCLUSION: EA can improve the gastrointestinal motility and symptoms in DGP rats, which may be related to its functions in downregulating PI3K/Akt/mTOR signaling to promote autophagy level of ICC. FAU - Zhang, Tian-Hua AU - Zhang TH AD - College of Acupuncture-Moxibustion-Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, China. FAU - Zhao, Sha-Tong AU - Zhao ST AD - College of Acupuncture-Moxibustion-Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, China. FAU - Li, Xiao-Yu AU - Li XY AD - College of Acupuncture-Moxibustion-Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, China. FAU - Xiao, Xiao-Juan AU - Xiao XJ AD - College of Acupuncture-Moxibustion-Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, China. FAU - Xiao, Le AU - Xiao L AD - College of Acupuncture-Moxibustion-Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, China. FAU - Wei, Xing AU - Wei X AD - College of Acupuncture-Moxibustion-Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, China. FAU - Peng, Yan AU - Peng Y AD - College of Acupuncture-Moxibustion-Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, China. LA - chi PT - English Abstract PT - Journal Article PL - China TA - Zhen Ci Yan Jiu JT - Zhen ci yan jiu = Acupuncture research JID - 8507710 RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - 0 (Blood Glucose) RN - I6G9Y0J1OJ (Phenolsulfonphthalein) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.1.1 (mTOR protein, rat) SB - IM MH - Rats MH - Animals MH - Rats, Sprague-Dawley MH - Proto-Oncogene Proteins c-akt/genetics/metabolism MH - *Interstitial Cells of Cajal/metabolism MH - Phosphatidylinositol 3-Kinases/genetics MH - *Electroacupuncture MH - Blood Glucose/metabolism MH - Phenolsulfonphthalein/metabolism MH - *Gastroparesis/genetics/therapy/metabolism MH - Signal Transduction MH - Paresis/metabolism MH - Pyloric Antrum/metabolism MH - TOR Serine-Threonine Kinases/genetics MH - Autophagy MH - Gastrointestinal Motility MH - *Diabetic Neuropathies MH - Mammals/metabolism OTO - NOTNLM OT - Autophagy OT - Cajal interstitial cells OT - Diabetic gastroparesis OT - Electroacupuncture OT - PI3K/Akt/mTOR signaling pathway EDAT- 2022/12/27 06:00 MHDA- 2022/12/28 06:00 CRDT- 2022/12/26 05:33 PHST- 2022/12/26 05:33 [entrez] PHST- 2022/12/27 06:00 [pubmed] PHST- 2022/12/28 06:00 [medline] AID - 10.13702/j.1000-0607.20211241 [doi] PST - ppublish SO - Zhen Ci Yan Jiu. 2022 Dec 25;47(12):1060-7. doi: 10.13702/j.1000-0607.20211241.