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Title: [Nuclear magnetic resonance-based metabolomics revealed metabolite profiles participate in intervention effect of refined moxibustion in gastric ulcer model rats].
Author: Wei GH, Yang ZB, Xie YF, Pei MR, Yang JL, Yu YJ, Cheng YB, Chen BH.
Journal: Zhen Ci Yan Jiu; 2021 Oct 25; 46(10):829-36. PubMed ID: 34698456.
Abstract:
OBJECTIVE: To investigate the effect of refined moxibustion on expression of gastric mucosal epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), and changes of metabolite profiles in gastric ulcer (GU) rats, so as to analyze its mechanism underlying improvement of GU. METHODS: Male SD rats were randomized into control, model, acupoint moxibustion groups (n=6 per group). The GU model was induced by cold-restraint stress. The ignited refined moxa was applied to bilateral "Liangmen" (ST21) and "Zusanli" (ST36) for 3 cones/acupoint, once daily for 7 days. Then, we employed 1H NMR-based metabolomics approach to analyze the metabolic profiles of serum and stomach tissue samples. The conventional histopathological changes of the gastric mucosa were observed by H.E. stain and the expressions of EGFR and VEGF in the gastric mucosa were detected by immunohistochemistry. RESULTS: Compared to the control group, the expression levels of EGFR and VEGF were significantly increased in the model group (P<0.01, P<0.05), and further notably up-regulated in the acupoint moxibustion group (P<0.001, P<0.01). Results of H.E. staining showed damage of the folds of gastric mucosa, disordered arrangement of the glands, infiltration of inflammatory cells and unclear structure of gastric mucosa in the model group, which was relatively milder in the acupoint moxibustion group. 1H-NMR technical analysis showed that in comparison with the control group, 11 and 11 metabolites in the stomach extract and plasma were increased, 10 in the gastric tissue and 3 in the plasma were decreased in the GU model group; while in comparison with the model group, 17 differently expressed metabolites in the gastric extract and 10 metabolites in the plasma restored to their levels of control group after the acupoint moxibustion intervention. These metabolites participate in 12 metabolic pathways including glycine, serine and threonine metabolism, glutathione metabolism, glycine metabolism, alanine, aspartic acid and glutamic acid metabolism, purine metabolism, glyoxylic acid and digarboxylic acid metabolism, biosynthesis of aminoacyl-tRNA, amino sugar and nucleotide sugar metabolism, cysteine and methionine metabolism, citrate cycle, pyruvate metabolism, and the mutual conversion of pentose and glucuronate，suggesting their involvement in moxibustion-induced improvement of GU. CONCLUSION: Refined moxibustion at ST21 and ST36 can up-regulate the expression of EGFR and VEGF in the gastric mucosa and lessen gastric mucosal injury, which may be related to its effects in reducing GU-induced metabolic disorders, including sugar, purine, amino acid, and phospholipid metabolism and antioxidant defense system. 目的：观察精灸对胃溃疡(GU)模型大鼠的干预作用，分析精灸干预GU的代谢响应机制。方法：将SD雄性大鼠随机分为对照组、模型组、精灸穴位组，每组6只。用束缚-冷应激法建立GU大鼠模型，精灸穴位组精灸大鼠双侧“梁门”“足三里”，每穴3壮，每天干预1次，连续干预7 d。用HE染色法观察大鼠胃黏膜组织病理形态，用免疫组织化学法检测大鼠胃黏膜组织表皮生长因子受体(EGFR)、血管内皮生长因子受体(VEGF)的表达，用核磁共振氢谱技术对大鼠血浆和胃黏膜组织进行代谢组学检测。结果：对照组大鼠胃黏膜结构清晰，层次分明，固有腺体排列整齐紧密，未见萎缩脱离或破损；模型组可见胃黏膜皱襞破损，腺体排列紊乱，有大量炎性细胞浸润，胃黏膜结构层次不清；精灸穴位组胃黏膜结构基本正常，腺体排列整齐，固有层细胞排列紧密，无明显炎性细胞浸润，整体修复情况优于模型组。与对照组比较，模型组胃黏膜组织中EGFR、VEGF表达水平明显升高(P<0.01，P<0.05)。与模型组比较，精灸穴位组大鼠胃黏膜组织中EGFR、VEGF表达明显升高(P<0.001，P<0.01)。精灸双侧“梁门”“足三里”可有效逆转GU大鼠血浆和胃黏膜组织中共26种与GU病理相关的特征性代谢物水平(P<0.05, P<0.01, P<0.001)，有效调节由GU造成的12条代谢通路的紊乱。结论：精灸“梁门”“足三里”可显著促进EGFR、VEGF的表达，全面调节由GU造成的代谢紊乱，包括能量代谢、糖代谢、嘌呤代谢、氨基酸代谢、磷脂代谢等，对胃溃疡具有一定的治疗效应。.

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