在前期研究基础上，提出“基于病证方结合的中医诊疗模式构建中医证候动物模型”的研究构想，通过寻求与证候相关疾病的关键病理环节选择合适的造模方法模拟临床特征和病理过程，并通过“以方测证”和“类证方反证”的方法动态地考察模型在不同时程证候属性。以临床常见的气阴两虚证为切入点，利用信息挖掘技术，发现益气养阴代表方生脉散所防治多种疾病的关键病理环节是缺氧和氧应激，继而发现慢性间歇性缺氧模型小鼠在一定阶段表现为：体重下降，摄食量减少，自发活动改变，心率加快、T 波持续性升高等心电图异常改变、出血时间缩短等，部分模拟了气阴两虚证的主要临床表现和由虚到瘀的病机演变过程，并伴随氧化应激异常等病理变化，生脉散可明显改善上述指征，从而初步验证了所提出的建模假说及慢性间歇性缺氧模型的气阴两虚证候属性。课题组正开展进一步的研究，以期为揭示气阴两虚证的科学内涵及深入阐释益气养阴代表方的作用机理提供可靠的实验与技术平台，并为证候动物模型的构建提供思路与方法借鉴。

A hypothesis has been proposed based on previous study that common pathological factor (s) of those diseases related with the syndrome can be selected to be preferable mode in the construction of animal model of syndrome. The animal model is in accordance with the clinical diagnosis and treatment mode based on integrated disease, syndrome and formula of traditional Chinese medicine (TCM). While macroscopic signs simulate main clinical features of the syndrome, dynamic changes must be in accordance with evolvement rule of the syndrome. The syndrome attribute of animal model can be determined by "Syndrome Differentiation through Formula Effect Assessment" and "Syndrome Distinguishment through Correlative Formula Effect Assessment" after corresponding formulae were administered. Our present study is focused on qi-yin deficiency syndrome (QYDS), which is one of common clinical syndromes. Previous data mining has shown that hypoxia and oxidative stress are considered as key pathological factors among diseases relative to QYDS based on Sheng-Mai-San (SMS), one of related representative fomula. Further study has found that mice exposed to intermittent hypoxia for certain time presented lackluster hair, dull looking hair, resistance, attacking, body weight loss, food intake decline, locomotive activity decrease, heart rate quickening and T-wave continuous elevating and bleeding time shortening, which not only shares the similarities with the characterization of major clinical features of QYDS, but also accords with the clinical fact that QYDS often accompanied with blood stasis. Meanwhile, abnormal oxidative stress was also observed in the model mice. SMS can significantly improve manifestations mentioned-above. The complex prescription is used to promote blood circulation by removing blood stasis. It shows unobvious effect except prolong the bleeding time. Thus the hypothesis was confirmed and the QYDS attribute of the chronic intermittent hypoxia animal model was also determined. Further investigation is in process to reveal the scientific meaning of QYDS and provide a reliable platform to elucidate the mechanism of SMS. This work may provide some new ideas or methods for constructing animal model of syndrome.

科学技术部国家“十一五”科技支撑计划（2008BAI51B03）：中药有效成分群关键技术研究，负责人：余伯阳；教育部中央高校科研专项基金（JKY2009006）：基于中医临床特点构建气阴两虚型冠心病动物模型的探索研究，负责人：余伯阳，柴程芝。