基于核磁共振代谢组技术研究电针胃经穴对胃黏膜损伤修复的脑胃响应机制

Gastric mucosal lesion is the initiating pathological process in many refractory gastric diseases. Many literatures indicate that acupuncture and moxibustion is significant curative effect for the treatment of the gastric mucosal lesion diseases. Our previous study indicated that acupuncture and moxibustion in the stomach meridian acupoints have very good prevention and cure effect in the gastric mucosal lesion diseases, which can regulate the expression of the related signal protein and a variety of ghrelin and so on. However, the overall mechanism of the gastric mucosal lesion repair promoted by acupuncture and moxibustion in the stomach meridian acupoints has not yet been revealed.The metabonomics is the research methods with whole concept of life science in recent years, which is correspond to the overall adjustment characteristic of the acupuncture and moxibustion.This project puts forward the hyposis of the meridian of foot yangming and stomach related with specific metabolic substances.By adopting the method of pathological morphology, molecular biology and nuclear magnetic resonance (NMR) metabonomics technology, to study the gastric mucosal morphology, ghrelin expression and the metabolic change of the brain tissue, cerebrospinal fluid,gastric mucosa, blood and urine in the gastric mucosal lesion rats treated with electroacupuncture in stomach meridian acupoints as a whole, organize, molecular and in vivo and in vitro level, to screen the specific biomarkers, to explore the response mechanism of the brain and stomach on the gastric mucosal lesion repair treated by electroacupuncture in stomach meridian acupoints,to reveal the related metabolic material basis between the meridian of foot yangming meridian and stomach, which is greatly significant to further expand the prevention and treatment of the gastric mucosa lesion by acupuncture and moxibustion and reveal the scientific connotation of the relationship with the meridian and viscera.

胃黏膜损伤是多种难治性胃病的始动病理环节，诸多文献表明针灸治疗胃黏膜损伤具有显著疗效。本课题组前期研究证实针灸胃经穴对胃黏膜损伤有很好的防治作用，可调节多种特异信号蛋白质和相关胃肠肽的表达等，然而针灸胃经穴促进胃黏膜损伤修复的整体调节机制尚未科学揭示。代谢组学是近年出现的具有生命科学整体观念的研究方法，与针灸整体调节特点相契合。本项目在前期研究基础上提出"足阳明经与胃相关具有特定代谢物质基础"假说，采用病理形态学、分子生物学方法和核磁共振代谢组学技术，从整体、组织、分子水平和在体、离体层面观察电针胃经穴对胃黏膜损伤大鼠胃黏膜形态、脑肠肽表达和脑组织、脑脊液、胃黏膜、血液、尿液代谢组的影响，筛选特异性代谢标记物，探讨电针胃经穴促进胃黏膜损伤修复的脑胃响应机制，阐明足阳明经与胃相关的代谢物质基础，这对于进一步拓展胃黏膜损伤疾病的针灸防治、揭示经脉脏腑相关的科学内涵具有重要意义。

胃黏膜损伤是临床常见的病理现象，是多种难治性胃部疾病的始动病理环节，积极防治胃黏膜损伤、促进胃黏膜损伤的及时修复是阻断难治性胃部疾病发生的重要途径。诸多文献和课题组前期研究结果表明针灸胃经穴对胃黏膜损伤具有很好的预保护和修复作用，然而针灸胃经穴干预胃黏膜损伤的响应机制尚未阐明。本项目在前期研究基础上继续开展了以下研究：① 电针胃经穴对胃溃疡大鼠胃黏膜组织的修复作用及血液、尿液、胃黏膜、大脑皮质、下丘脑和延髓代谢组学的影响；② 电针胃经穴对胃溃疡大鼠胃黏膜的时效修复作用及胃黏膜细胞增殖因子的时效表达；③ 电针胃经穴对胃溃疡大鼠血液、大脑皮质、延髓、胃黏膜、肝、肾代谢组的时效影响；④电针胃经穴对慢性萎缩性胃炎大鼠胃黏膜的修复作用和胃黏膜细胞增殖因子表达以及血液、尿液、胃黏膜、大脑皮质、延髓代谢组学的影响。.研究结果表明：① 电针胃经穴能有效促进胃黏膜损伤的修复，可调节胃黏膜细胞增殖因子的表达，且具有一定的时效关系；② 电针胃经穴对胃溃疡大鼠血液、胃黏膜、大脑皮质、肝、肾和延髓代谢物谱有回复正常的趋势，可调节多种特异代谢物的表达，其干预效应具有一定的时效规律；③ 电针胃经穴对慢性萎缩性胃炎大鼠胃黏膜损伤修复有一定的促进作用，可调节多种胃黏膜细胞增殖因子的表达，对慢性萎缩性胃炎大鼠血液、尿液、胃黏膜、大脑皮质、延髓代谢物谱有回复正常的趋势，可有效调节慢性萎缩性胃炎引起的脂代谢和肠道菌群代谢紊乱，并对脑内神经递质的功能有一定的恢复作用。.本项目采用系统生物学的核磁共振代谢组技术，从整体、组织和分子水平动态的观察了电针胃经穴对胃黏膜损伤大鼠脑、胃、肝、肾组织和血液、尿液的代谢物谱的表达，筛选特异性代谢物，探讨电针胃经穴干预胃黏膜损伤修复的代谢响应位点，阐明了足阳明胃经与胃相关的特异代谢物质基础，这对于进一步拓展胃黏膜损伤疾病的针灸防治、揭示经脉脏腑相关的科学内涵具有重要意义。