循经取穴治疗原发性高血压的宿主代谢-肠道微生物Cross-talk机制研究

Acupuncture at acupoints on involved meridian (AAOIM) serves as one of the most important therapeutic principle in clinics. Essential hypertension is an independent risk factor for heart disease, stroke, renal failure and other severe diseases, which is rather harmful to one’s health. A large number of RCTs have shown that AAOIM was effective in treating essential hypertension, and some of the findings also suggested that the metabolic environment was closely related to hypertension. Thus, metabolomics mechanism of acupuncture treatment for hypertension has been attracting much more attention from researchers concerned. As the extension of our previous studies, this research sticks to the theory of "host metabolism and flora Cross-talk", holding the hypothesis that acupuncture reduces blood pressure of the patients with hypertension by regulating Cross-talk host metabolism and intestinal microflora. Taken the patients with essential hypertension as the carrier, AAOIM is employed to reduce BP, and the regulating action of AAOIM for Cross-talk host metabolism and intestinal microflora will be explored by applying NMR metabolomics techniques and PCR-DGGE molecular ecology techniques, so as to improve acupuncture clinical efficacy and promote the modernization and globalization of acupuncture through revealing the biological mechanisms of the antihypertensive action of acupuncture from a new perspective and explaining the scientific connotation of AAOIM effect.

循经取穴是针灸临床最重要的选穴原则。原发性高血压是心脏病、中风、肾功衰等重大疾病的独立危险因素之一，严重危害人类的身体健康。大量的临床RCT研究显示循经取穴针灸治疗原发性高血压疗效肯定，不少研究结果也提示机体代谢异常与高血压发病密切相关。因此，针灸治疗高血压的代谢组学机制已越来越受到研究者的重视。本课题在前期研究的基础上，基于“宿主代谢与菌群Cross-talk”理论，紧密围绕“针刺通过调控宿主代谢与肠道微生态之间的Cross-talk发挥降压作用”的工作假说，以原发性高血压病患者为研究载体，应用循经取穴针刺治疗，采用NMR代谢组学技术和PCR-DGGE分子生态学技术，深入探讨循经取穴针刺对原发性高血压患者代谢和肠道微生态之间Cross-talk的调控作用，以期从全新角度深入揭示针刺降压的生物学机制、阐释循经取穴针刺效应的科学内涵，以更好地提高针灸临床疗效、促进针灸学的现代化、国际化发展。

针刺治疗原发性高血压（EH）具有一定的临床疗效，但针刺降压的机制仍不明确。本研究在评价针刺治疗EH临床疗效的基础上，通过对血浆物质代谢及肠道微生物物质的检测、提取，挖掘针刺治疗EH的物质代谢信息特征，发现EH患者与健康人相比，其肠道优势菌群组成中存在帕古菌门(Parcubacteria)、绿弯菌门(Chloroflexi)；在菌群组成方面，高血压患者厚壁菌门的Blautia属、Anaerostipes属比重显著降低。针刺后帕古菌门(Parcubacteria)、绿弯菌门(Chloroflexi)所占比重均降低；在菌群组成上，针刺后柔膜菌门的丹毒丝菌科、微球菌科比重显著降低。非穴针刺后，优势菌群比及菌群组成并未发生显著变化。而在物质代谢方面，高血压患者代谢模式偏离健康状态，其关键代谢小分子为缬氨酸、异亮氨酸、苯丙氨酸、酪氨酸、亮氨酸、瓜氨酸、次黄嘌呤、苏氨酸、果糖、尿酸；经穴针刺降压的关键代谢小分子为山梨酸、草酰乙酸、异亮氨酸、亮氨酸。确定三羧酸循环与缬氨酸、亮氨酸、异亮氨酸的生物合成与分解可能是针刺降压调控的关键代谢通路。非穴组针刺后并未引起代谢模式的改变。本研究从物质代谢及肠道菌群的角度对针刺降压的机制做了进一步阐释，为针刺的临床应用提供更为充分的科学依据。