麻黄细辛附子汤（MXF）是治疗肾阳虚外感的经典方剂，但因含有毒性药材极大地影响其在临床使用。基于我们前期研究并根据中医“有故无殒”治法思想推测，MXF在正常、病证结合模型动物上表现出明显的量-毒关系不一致现象是与MXF的毒/效组分对机体心肌细胞线粒体细胞色素C氧化酶（Cyt-CO）调控有关。为了验证假说，在前期成熟的肾阳虚外感小鼠模型基础上，从体外、体内比较MXF不同剂量提取物对正常、病证结合模型小鼠的心肌细胞毒性，研究心肌线粒体Cyt-CO调控的凋亡通路，超分辨共聚焦显微镜检测Cyt-CO分布及表达，采用组织化学法检测Cyt-CO活性、并检测Cyt-C、caspase-3等的mRNA和蛋白表达；同时比较与调控炎症有关先天免疫应答TLR7信号通路的药效变化。基于证-毒-效关联技术，力图揭示MXF多成分在机体不同生理、病理状态下靶向毒性/药效的非线性变化特征和中药复方双向调节作用的分子机制。

Mahuang-Xixin-Fuzi decoction (MXF) is a classical prescription for exogenous disease with kidney yang deficiency, but which has limited clinical application due to toxic herbal components. According to our previous studies and the effect-toxicity theory of traditional Chinese Medicine, we hypothesize that the discrepancy between dose and toxicity is related to the regulation of toxic/effective herbs in MXF on cytochrome C oxidase (Cyt-CO) in cardiomyocytes. Based on the successful mouse model of exogenous fever with kidney yang deficiency, we plan to compare the toxicity in cardiomyocytes of normal and syndrome model mice with the extract of different MXF doses in vitro and in vivo, investigate apoptosis pathway modulated by Cyt-CO in mitochondria, determine the distribution and expression of Cyt-CO with superresolution confocal microspectroscopy, detect the activity of Cyt-CO with histochemistry, test the expression of mRNA and protein of Cyt-C, caspase-3, and etc, and evaluate anti-inflammatory and anti-apoptosis effect involving TLR7 signalling pathway. In terms of syndrome-toxicity-effect combined technique, we strive to unveil the non-linear characteristics of toxicity/effect under the circumstances of different physiological and pathological status and reveal the molecular mechanism of bidirectional regulation of Chinese medicine.