基于ENS-ICC-SMC网络探讨GERD复发患者中虚气逆证及中药干预机制

High recurrence rate of gastroesophageal reflux disease (GERD) is a serious trouble in clinic. However, there is little modern medicine to prevent recurrence of GERD. Traditional Chinese medicine (TCM) has good curative effect and less side effect on GERD recurrence. To our knowledge little domestic research is reported on a particular subject of this area. Besides, system research on the correlation between TCM syndrome of GERD recurrence and esophageal neural regulation dysfunction mechanism has not been reported as yet. This project is a good chance to seize the combination of TMC and Western Medicine. On the basis of the completed National Natural Science Foundation of china (81173392), we take the most commol/Lon syndrome in patients with GERD recurrence, the imaginary inverse gas card as a starting point, from the levels of clinic, animal and molecular cell to explore: ① The correlation between the imaginary inverse gas card and the ENS-ICC-SMC network dysfunction and its mechanism in patients with GERD recurrence. Whether the VIP and NO are achieved by activating ICC first in patients with GERD recurrence. How do ICCs regulates the relaxation and contraction movement of LES which is dominated by nerve. What are the modern mechanisms about the correlations of GERD inflammol/Latory factors, ENS and ICC cells. ③ The mechanism of ICC pacing induced by Jianpiliqi herbs may reveal new targets of ancient prescriptions. And it is expected to make the TCM syndrome objective and to open a new way to overcome the high recurrence rate of this disease by TCM.

胃食管返流病高复发率是临床亟待解决的难题。如何预防复发是现代医学的薄弱环节。中医中药抗GERD复发疗效好，副作用少，但国内这方面基础研究很薄弱。在GERD复发中医证以及与食管神经调控失调机制方面的深入研究尚未见报道。本项目抓住这一中西医结合的良好切入点，在刚刚完成的国家自然科学基金（81173392）基础上，拟从临床、整体动物和细胞分子水平三个层面，以GERD复发患者最常见的中虚气逆证为切入点，探索：①GERD复发患者中虚气逆证与ENS-ICC-SMC网络失调机制相关性；②GERD复发患者VIP、NO是否是通过首先激活Cajal间质细胞实现的？ICC如何参与调节神经支配的LES舒缩运动？GERD炎症因子与ENS、ICC的相关性如何？③健脾理气药诱发ICC起搏机制。揭示古方作用新靶点，可望为本病中医证的客观化，为中医中药攻克本病高复发率难题开辟新路子。

胃食管反流病是消化系统常见病，在全球范围内发病率逐年上升，目前以质子泵抑制剂为主的西药治疗约40%-50%的患者无效或停药后复发.中医中药在该领域有独特优势但临床基础研究十分薄弱。ENS-ICC-SMC网络与本病中虚气逆证的相关性国内外均未见报道。.我们以本病复发者最常见的中虚气逆证为切入点，对220例患者进行了前瞻性比较研究，发现血浆VIP、NO、NOS参与了其发生发展，且与本病中医证有着明显的相关性。66例NERD和93例RE中虚气逆证患者使用六君子汤合旋覆代赭汤治疗，中药组临床疗效明显优于西药组，复发率低于西药组，中药组治疗后血浆VIP、NO水平显著低于西药组；NF-κB、IL-6、IL-8、IL-9下降比西药组尤为明显。对82例难治性胃食管反流病脾虚证患者行PCR-RFLP基因分型，发现PPI联合中药治疗对CYP2C19基因强代谢型疗效更为显著，该项研究被中国中西医结合杂志评审专家誉为“开我国中西医结合临床治疗研究的先河”。. 我们在成功建立RE大鼠病证结合动物模型基础上，开展了六君子合旋覆代赭汤对RE大鼠食管ICC及SCF/c-kit通道的影响研究，发现中药古方是通过促进c-kit、SCF mRNA及其蛋白的表达，使其受损的ICC恢复正常，进而调节LES抗反流的作用机理 。我们在成功建立六君子合旋覆代赭汤含药血清质量标准的基础上，首次探讨了六君子汤合旋覆代赭汤含药血清对大鼠胃Cajal间质细胞活性及钙离子浓度的影响，结果发现，六君子汤合旋覆代赭汤可增强ICC内Ca2+浓度，从而提高ICC活性发挥其抗胃食管反流病作用。. 本项目已发表21篇学术论文，其中SCI 8篇，北大中文核心期刊9篇，培养5名硕士，其中一名获得江苏省优秀硕士论文。成果为本病中医中虚气逆证的客观化和揭示六君子汤合旋覆代赭汤古方抗胃食管反流病复发作用机理及临床药物开发奠定了基础，可望获得巨大的社会经济效益。