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  • Title: [Electroacupuncture regulates glucose metabolism disorder through PI3K/Akt/GSK3β signaling pathway in rats with depression].
    Author: Lu YJ, Shao C, Zhang S, Shi W, Li L, Zhao JJ.
    Journal: Zhen Ci Yan Jiu; 2023 Mar 25; 48(3):247-52. PubMed ID: 36951076.
    Abstract:
    OBJECTIVE: To explore the mechanism of electroacupuncture (EA) at "Zusanli" (ST36) on improving glucose metabolism disorder in chronic restraint induced depressed rats. METHODS: A total of 30 male SD rats were randomly divided into control, model and EA groups, with 10 rats in each group. The depression model was established by chronic restraint 2.5 h each day for 4 weeks. For rats in the EA group, EA stimulation (1 mA, 2 Hz, 30 min) was applied to bilateral ST36 during the modeling period, once a day for 4 weeks. The body weight of the rats was recorded before and after modeling. The behavior of rats was observed by sugar-water preference and forced swimming after modeling. The contents of glucose and glycosylated albumin in serum were determined by biochemical method. The histopathological morphology and liver glycogen content were observed by HE and PAS staining. The expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylated (p)-PI3K (p-PI3K), protein kinase B (Akt), p-Akt, glycogen synthase kinase-3β (GSK3β) and p-GSK3β proteins in liver were determined by Western blot. RESULTS: Compared with the control group, the weight increment and sugar-water preference index decreased (P<0.01), the immobile swimming time was prolonged (P<0.01), the glucose and glycosylated albumin contents in serum increased (P<0.05), the expression of p-Akt protein and the ratio of p-Akt/Akt in liver tissues decreased (P<0.001), the expression of p-GSK3β protein and the ratio of p-GSK3β/GSK3β in liver tissues increased (P<0.01,P<0.001) in the model group. Compared with the model group, the weight increment and sugar-water preference index increased (P<0.05), the immobile swimming time was shortened (P<0.05), the glucose and glycosylated albumin contents in serum decreased (P<0.05), the expressions of p-PI3K and p-Akt proteins and the ratio of p-PI3K/PI3K and p-Akt/Akt in liver tissues increased (P<0.05), the expression of p-GSK3β protein and the ratio of p-GSK3β/GSK3β in liver tissues decreased (P<0.01) in the EA group. HE staining showed that the structure of the hepatic lobule was intact, no obvious inflammatory cell infiltration or fibrosis was observed in the lobule and interstitium, and no abnormalities were observed in the small bile duct, portal vein and artery in the portal area. PAS staining showed that the intensity of staining from the center of the hepatic lobule to the periphery of the hepatic lobule was gradually enhanced in the blank group, that is, the glycogen-rich granules in the hepatic cells were gradually increased; most of the hepatocytes were light colored and glycogen was lost significantly in the model group; while the intensity of hepatocyte staining increased, the staining intensity of the perilobular zone was weaker than that in the blank group, and the glycogen particles partially recovered in the EA group. CONCLUSION: EA intervention can regulate glucose metabolism disorder in chronic restraint induced depressed rats through PI3K/Akt/GSK3β signaling pathway. 目的：探讨电针“足三里”改善应激后抑郁大鼠糖代谢紊乱的作用机制。方法：SD大鼠随机分为空白组、模型组、电针组，每组10只。采用慢性束缚应激复制抑郁大鼠模型。电针组造模期间同时进行双侧“足三里”电针干预，每次30 min，每日1次，持续4周。造模前后记录大鼠体质量并计算体质量增加量；造模结束后行糖水偏好实验、强迫游泳实验观察大鼠行为学；生化法检测大鼠血清中葡萄糖含量及糖化白蛋白水平；HE染色、PAS染色观察大鼠肝脏组织病理形态及肝糖原含量；Western blot法检测肝脏组织中磷脂酰肌醇3-激酶(PI3K)、磷酸化(p)-PI3K、蛋白激酶B(Akt)、p-Akt、糖原合成酶激酶-3(GSK3β)、p-GSK3β蛋白表达量。结果：与空白组相比，模型组大鼠体质量增加量、糖水偏好指数降低(P<0.01)，游泳不动时间延长(P<0.01)，血清中葡萄糖含量及糖化白蛋白水平升高(P<0.05)，肝脏组织中p-Akt蛋白表达量及p-Akt/Akt比值降低(P<0.001)，p-GSK3β蛋白表达量及p-GSK3β/GSK3β比值升高(P<0.01，P<0.001)；与模型组相比，电针组大鼠体质量增加量、糖水偏好指数明显升高(P<0.05)，游泳不动时间缩短(P<0.05)，血清中葡萄糖含量及糖化白蛋白水平降低(P<0.05)，肝脏组织中p-PI3K、p-Akt蛋白表达量及p-PI3K/PI3K、p-Akt/Akt比值升高(P<0.05)，p-GSK3β蛋白表达量及p-GSK3β/GSK3β比值降低(P<0.01)。HE染色显示，各组大鼠肝组织小叶结构完整，小叶和间质内未见明显炎性细胞浸润或纤维化，汇管区内小胆管、门脉及动脉未见异常。PAS染色显示，空白组大鼠肝组织自肝小叶中心(即小叶3带)至小叶周围带染色程度渐增强，即肝细胞富含糖原颗粒渐增多；模型组肝细胞大部分着色浅淡，糖原脱失显著；电针组肝细胞着色增加，肝小叶周围带染色强度较空白组弱，糖原颗粒部分恢复。结论：电针“足三里”可以通过PI3K/Akt/GSK3β信号通路调节慢性束缚致抑郁大鼠的糖代谢紊乱。.
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