基于ACE2/Ang 1-7/Mas轴的人参总皂苷多系统保护作用研究

Renin angiotensin system (RAS) is one of the most important humoral regulation systems. The ACE/Ang II/AT1 axis, which would cause multy systems injury when activating excessively, was considered to play the major role of the physiological function of RAS traditionally. The ACE2/Ang 1-7/Mas axis, which was discovered after 2000, has inhibiting effect on the multy systems injury, and has became a research hotspot of new drugs developing. Panax ginseng C. A. Mey. is a kind of famous and precious traditional Chinese medicine, of which the effective part is ginsenoside. Similar to the ACE2/Ang 1-7/Mas axis, ginsenoside has multy systems protection, including circulation system, urinary system, digestive system, endocrine system and so on. Therefore, activation of the ACE2/Ang 1-7/Mas axis may be the mechanism of the multy systems protection of ginsenoside. With our previous achievement, we have designed four experiments to test this hypothesis in this project, using spontaneously hypertensive rat, Apo E knockout mice, db/db mice and ACE2 knockout mice. It's going to provide new ideas for the pharmacological research of the multy effects of ginseng and the other traditional Chinese medicines. It's the first time to research the mechanism of traditional Chinese medicine effects with both the holistic/dialectical theory of traditional Chinese medicine and the modern medical theory, which is also an important innovation to the theory of integrated traditional and western medicine.

肾素-血管紧张素系统是机体重要的体液调节系统，传统上认为其生理功能是基于ACE/Ang II/AT1轴，过度激活则会造成多系统损伤。2000年后发现的ACE2/Ang 1-7/Mas轴能抑制这种多系统损伤，已成为新药研发的热点。人参是我国名贵中药材，人参皂苷是其主要有效部位，对人体循环、泌尿、消化、内分泌等多个系统均具有保护作用，恰好与ACE2/Ang 1-7/Mas轴的多系统保护作用相似，提示人参皂苷的多系统保护作用机制可能是基于该轴。本项目在前期工作基础上，采用自发性高血压、高血脂、高血糖动物模型及ACE2基因敲除动物对该假说进行验证，为人参及其它具有多重作用的中药的药理学研究提供全新思路。首次运用现代医学理论结合中医学的整体和辨证思维解释中药的功效，是对中西医结合理论的一个创新。

肾素-血管紧张素系统是机体重要的体液调节系统，传统上认为其生理功能是基于ACE/Ang II/AT1轴，过度激活则会造成多系统损伤。2000年后发现的ACE2/Ang 1-7/Mas轴能抑制这种多系统损伤，已成为新药研发的热点。人参是我国名贵中药材，人参皂苷是其主要有效部位，对人体循环、泌尿、消化、内分泌等多个系统均具有保护作用，恰好与ACE2/Ang 1-7/Mas轴的多系统保护作用相似，提示人参皂苷的多系统保护作用机制可能是基于该轴。本项目采用自发性高血压、高血脂、高血糖动物模型及ACE2基因敲除动物对该假说进行验证。.研究证实：人参总皂苷、人参皂苷Rb1和人参皂苷Re均可以通过增强ACE2/Ang 1-7/Mas轴功能，抑制相关组织中的炎症、氧化应激和纤维化，在自发性高血压、高血脂、高血糖的动物模型中，发挥多系统（循环系统、消化系统、泌尿系统）保护作用。这种保护作用不依赖于对异常升高的血压、血脂和血糖的下调。Mas受体抑制剂A779不能逆转这3类皂苷的多系统保护作用，说明人参皂苷通过增强ACE2/Ang 1-7/Mas轴功能发挥多系统保护作用的时候，上调ACE2，降解Ang II的作用是主要的，上调Ang 1-7，激活Mas受体的作用是次要的。此外，在ACE2基因敲除鼠体内，人参皂苷的多系统保护作用被阻断，说明ACE2蛋白上调是人参皂苷在体内发挥保护作用的关键机制，若ACE2基因缺失，则人参皂苷的多系统保护作用可能被逆转。.本研究具有以下两方面的科学意义：一是为人参及其它具有多重作用的中药的药理学研究提供全新思路，为研发更多防治高血压、高脂血症和糖尿病的中药新药提供理论依据；二是首次运用现代医学理论结合中医学的整体和辨证思维方法解释中药的功效，是对中西医结合理论的一个创新。