Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, Shandong, China.
Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, Shandong, China.
Neuromodulation. 2022 Dec;25(8):1106-1114. doi: 10.1016/j.neurom.2021.10.003. Epub 2021 Dec 18.
Lack of interstitial cells of Cajal (ICC) and neuropathy were the most possible pathological mechanisms of diabetic gastroparesis. Gastric electrical stimulation (GES) is a promising way to treat gastroparesis. This study aimed to explore the impact of GES on ICC together with enteric neurons in diabetic rats and the possible mechanisms involved.
A total of 60 rats were randomized into six groups, including the normal control group, diabetic group (DM), diabetic with sham GES group (DM + SGES), and three groups of diabetic rats with GES (DM + GES1, DM + GES2, and DM + GES3). The proliferation of ICC and expressions of 5-hydroxytryptamine (serotonin) receptor 2B (5-HT2B), neuronal nitric oxide synthase (nNOS), choline acetyltransferase (CHAT), protein gene product 9.5, and glia cell line-derived neurotrophic factor (GDNF) in the antrum of the stomach were evaluated by immunofluorescence staining or Western blot. The levels of 5-HT in blood and tissue were determined by enzyme-linked immunosorbent assay.
The proliferation of ICC was significantly reduced in the DM group, together with the DM + SGES group, but increased in the three DM + GES groups. The expression of 5-HT2B was decreased in the DM group and enhanced in the DM + GES groups. Similarly, the levels of 5-HT in the blood and distal stomach tissue were increased in the DM + GES groups. Both nNOS labeled neurons and CHAT-positive neurons were reduced in the myenteric plexus of the DM group, whereas these neurons were dramatically increased the in DM + GES groups. The expression of GDNF protein in the diabetic rats was down-regulated, whereas GES increased the expression of GDNF.
GES improves the proliferation of ICC possibly related with the 5-HT/5-HT2B signal pathway and alters the enteric nervous system partly though the GDNF expression.
缺乏 Cajal 间质细胞（ICC）和神经病变是糖尿病胃轻瘫最可能的病理机制。胃电刺激（GES）是治疗胃轻瘫的一种有前途的方法。本研究旨在探讨 GES 对糖尿病大鼠 ICC 及其相关的肠神经元的影响及其可能的机制。
将 60 只大鼠随机分为六组，包括正常对照组、糖尿病组（DM）、糖尿病假 GES 组（DM+SGES）和三组糖尿病 GES 组（DM+GES1、DM+GES2 和 DM+GES3）。通过免疫荧光染色或 Western blot 评估胃窦 ICC 的增殖以及 5-羟色胺（5-HT）受体 2B（5-HT2B）、神经元型一氧化氮合酶（nNOS）、胆碱乙酰转移酶（CHAT）、蛋白基因产物 9.5（PGP9.5）和胶质细胞源性神经营养因子（GDNF）的表达。通过酶联免疫吸附试验测定血液和组织中 5-HT 的水平。
DM 组和 DM+SGES 组 ICC 的增殖明显减少，但在三个 DM+GES 组中增加。5-HT2B 的表达在 DM 组中降低，在 DM+GES 组中增强。同样，DM+GES 组血液和远端胃组织中的 5-HT 水平也升高。DM 组肌间神经丛中 nNOS 标记神经元和 CHAT 阳性神经元减少，而 DM+GES 组中这些神经元显著增加。糖尿病大鼠 GDNF 蛋白的表达下调，而 GES 增加了 GDNF 的表达。
GES 改善 ICC 的增殖，可能与 5-HT/5-HT2B 信号通路有关，并通过 GDNF 表达部分改变肠神经系统。
