基于“脾主运化”理论探讨运脾消积法对厌食症幼龄大鼠肠道微生态及宿主代谢的干预机制

In recent years, with the improvement of living standards of our society, the incidence of anorexia upward trend, this phenomenon has aroused wide attention of the medical profession.TraditionalChinese medicine in the treatment of anorexia in children has accumulated a wealth of experience, mechanism study focused on anorexia in proteomics, immune proteomics etc, but for the intestinal microecology in domestic research is still rarely reported. The study found that structural imbalance of intestinal microflora is a key factor in the occurrence and development of anorexia.On the basis of the preliminary study, the project in the etiology and simulation preparation of anorexia rats as the research object, the TCM pathogenesis of essence of anorexia, intestinal micro ecological homeostasis and traditional Chinese medicine"the spleen's governing transportation theory " the three combined,to these as athe breakthrough point, for the first time using the most advanced method of PCR-DGGE and 1HNMR metabonomic studies of molecular biology techniques of Yunpi Xiaoji method about anorexia model of intestinal micro ecology and host metabolic phenotypes of influence.The internal mechanism of interpretation of the law, rich scientific connotation of Xiaoer kaiwei ZengShi mixturewhich is the representative of the yunpi xiaoji method in the treatment of anorexia, and put forward new ideas and new ways for the development of the treatment of anorexia.

近年来，随着我国社会生活水平的提高，小儿厌食症呈上升趋势，引起了医学界的广泛重视。中医药在治疗小儿厌食症方面积累了丰富的经验，关于厌食症的机理研究主要集中在蛋白组学、免疫组学等方面，但对于肠道微生态学研究国内仍少见报道。研究发现肠道微生态结构失调是厌食症发生和发展的关键因素。本项目拟在前期研究基础上，以病因模拟法制备的厌食症模型大鼠为研究对象，将本病的中医病机实质、肠道微生态稳态及中医“脾主运化”理论三者结合起来，以此为切入点，首次采用目前最先进的PCR-DGGE法及1H NMR的代谢组学等分子生物学技术，探讨运脾消积法对厌食症模型肠道微生态及宿主代谢表型的影响，诠释该法的内在机理，丰富以运脾消积法为代表方的小儿开胃增食合剂治疗厌食症的科学内涵，提出和发展治疗厌食症的新思路和新途径。

目的：基于“脾主运化”理论探讨运脾消积法对厌食症幼龄大鼠肠道微生态及代谢组学的影响。方法：以病因模拟法建立小儿厌食症（Children Anorexia；CA）幼龄大鼠模型，记录大鼠摄食量和体重变化；分组干预：空白组（A）、模型组（B）、阳性对照组（江中健胃消食片，C）、小儿开胃增食合剂低（D）、高剂量组（E）；干预后运用光镜、16s RNA及LC-MS检测法，分别对胃窦及空肠、肠道菌群及尿液代谢物进行观察、鉴定分析。结果：Ⅰ摄食量和体重变化，与A组比较，B组显著减少（P＜0.05）；干预后与B组比较，C、E组显著增加（P＜0.05）。Ⅱ与A组比较，B组胃窦、肠黏膜层炎性细胞浸润，平滑肌细胞紊乱，绒毛变短变宽；炎症评分显著增高（P＜0.05）。干预后与B组比较，各给药组胃窦、空肠炎性细胞显著减少，黏膜趋于完整，炎症评分显著下降（P＜0.05）；C、E组绒毛增长，宽度减低，隐窝加深（P＜0.05）。Ⅲ模型大鼠中明显失调的肠道菌群OUT、丰度、多样性、迷踪菌门、棒状杆菌属、Odoribacter属、YRC22属、普雷沃菌属、Jeotgalicoccus属、瘤胃球菌属、rc4−4属以及三类功能菌群，干预后均向正常或保护方向恢复。ⅣB、C、D、E组分别有29、45、29、48个代谢物发生了变化，所涉及的代谢通路分别为9、25、14、19条。结论：Ⅰ运脾消积法方药小儿开胃增食合剂能显著改善CA大鼠摄食量减少及体重下降；Ⅱ高脂高蛋白饮食能促发胃窦及空肠黏膜损伤，造成炎性细胞浸润，进而导致CA发生，该合剂通过保护胃肠黏膜及绒毛结构的完整性治疗CA。Ⅲ模型大鼠肠道菌群多样性发生了明显改变，包括保护性和病理损伤性改变。该合剂通过调整肠道菌群结构、抑制或促进特定菌属生长、明显加强保护性菌属的有益改变，减弱有害性菌属的损伤改变，调节肠道菌群功能，促进菌群多样性和功能恢复正常。ⅣCA大鼠代谢失调，该合剂使其代谢发生恢复性和保护性变化，主要涉及肠道菌群代谢、脂质代谢、氨基酸代谢、三羧酸循环、磷酸戊糖代谢途径。

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