基于COX-2及相关信号通路研究针灸对慢性萎缩性胃炎大鼠的胃黏膜保护机制

Chronic atrophic gastritis (CAG) and precancerosis are the inevitable initial links that gastric cancer has to go through. Modern medicine has no specific drug therapeutic to CAG, which cannot fundamentally reverse gastric mucosa atrophy and the dysfunction of gastric. Consider how to mobilize the body's cells themselves of adaptive protection mechanism to reduce the cell damage, is gradually becoming the CAG precancerous disease prevention and control of the important topics at home and abroad. Numerous researches indicate acupuncture and moxibustion have strong prevention and cure effect for CAG. Our previous clinical and experimental researches suggested acupuncture and moxibustion have strong preventing and cure for chronic atrophic gastritis and precancerosis. However, the molecular mechanisms of acupuncture and moxibustion on CAG gastric mucosa protection have not been fully revealed. This project make a quantitative analysis and comparative study between acupuncture and moxibustion on the protection of CAG gastric mucosa, by using pathological image analysis technology and multivariate data mining technology, on the perspective of gastric mucosa tissue pathology, gastric mucous membrane barrier function, gastric mucosa secretion, gastric mucosa protection material and cell signal transduction (inflammation, cell proliferation and apoptosis), base on the previous researches and tracking the latest progress of the CAG gastric mucosal protection mechanism, make COX-2 and related signaling pathway research as the breakthrough point. This research will provide scientific experimental proofs for applying moxibustion to treat chronic atrophic gastritis and precancerosis.

慢性萎缩性胃炎（CAG）是胃癌的关键病理环节，现代医学对CAG无特异性治疗药物，无法从根本上逆转胃黏膜的萎缩及由此引发的胃功能损伤。目前国内外考虑如何调动机体细胞自身的适应性保护机制以减少细胞损伤，正逐渐成为CAG等癌前疾病防治的重要课题。诸多研究表明针灸治疗慢性萎缩性胃炎具有显著疗效。本课题组前期研究证实针灸可调节多种相关胃肠肽的表达，逆转CAG癌前病变，然而针灸对CAG胃黏膜保护作用的分子机制尚未完全揭示。本研究在前期基础上，跟踪CAG胃黏膜保护机制的最新进展，以COX-2及相关信号通路研究为切入点，从胃黏膜组织病理学、胃黏膜屏障功能、胃黏膜分泌功能、胃黏膜保护物质与细胞信号转导（炎症反应、细胞增殖与凋亡）等角度，利用病理图像分析技术和多元数据挖掘技术，将针刺与艾灸对CAG胃黏膜保护作用作定量分析和对比研究，为针灸干预CAG癌前病变、阻断其向胃癌进展的临床研究和推广应用提供科学依据。

本课题组前期研究证实针灸可调节多种相关胃肠肽的表达，然而针灸对CAG胃黏膜保护作用的分子机制尚未完全揭示。本研究在前期基础上，以COX-2及相关信号通路研究为切入点，从胃黏膜组织病理学、胃黏膜屏障功能、胃黏膜分泌功能、胃黏膜保护物质与细胞信号转导（炎症反应、细胞增殖与凋亡）等角度，利用病理图像分析技术和多元数据挖掘技术，将针刺与艾灸对CAG胃黏膜保护作用作定量分析和对比研究。研究发现，针刺与艾灸均可改善大鼠的一般行为学及病理学，下调胃黏膜中COX-2的表达，降低IL-6、IL-8、IL-1β基因的表达量，抑制胃黏膜炎性损伤从而治疗或延缓CAG的发生、发展，两者均有抑制白细胞介素表达的作用；针刺与艾灸均可升高CAG大鼠胃组织EGF、EGFR表达，对胃黏膜的增殖修复有积极作用；针刺与艾灸均能通过改善CAG胃黏膜细胞凋亡，降低NF-κΒ、Bcl-2的表达量，达到防治CAG的目的；针刺与艾灸对正常SD大鼠胃组织代谢存在差异,两者都影响了胃组织的能量代谢、氨基酸代谢、核酸代谢、抗氧化相关代谢，艾灸对胃组织能量代谢的调控作用更强；针刺与艾灸对CAG大鼠胃组织代谢存在差异，艾灸调节有利于CAG大鼠胃黏膜的修复和免疫力的提高。但是，从本次实验结果看，暂未发现与针刺治疗慢性萎缩性胃炎相关的的差异代谢物，可能针刺效应的代谢作用途径有别于艾灸，其结果有待于进一步分析。以上研究为针灸防治萎缩性胃炎，干预CAG癌前病变、阻断其向胃癌进展的临床研究和推广应用提供科学依据。