太阴病（脾阳虚证）"欲解时"与环磷酸腺苷变化的相关性及理中汤干预研究

The result of The National Natural Science Foundation of China project "Correlated Study on The Recovery of Tai yang Disease(Wind Cold Superficies Syndrome) and Interleukin" by research group shows: Interleukin's content and rhythm changes of model animals are closely related with The Recovery of Tai yang Disease(Wind Cold Superficies Syndrome). Based on this, according to spleen to transport for the source of qi and blood biochemical theory in Traditional Chinese medicine, carry out the correlation research of cAMP' s change and The Recovery of Tai yin Disease , to further explore the correlation with expression of cAMP and rhythm changes in model animals of Tai yin Disease(Spleen-Yang Deficiency Syndrome) occurrence and development regularity; selects blood amylase and D-xylose concentration research the spleen transport function of the state in The Recovery of Taiyin Disease; detects peripheral blood, discusses the correlation between qi and blood biochemical changes with Taiyin Disease; Through the observation of the stomach intestine morphology of pancreas and other organs，study histopathological changes of Taiyin Disease(Spleen-Yang deficiency syndrome).Explain physiological and pathological basis of The Recovery of Taiyin Disease from the body's energy metabolism, digestive function, qi and blood biochemical changes. And through study of the Lizhong decoction impact on index of correlation with cAMP ,etc. in The Recovery of Taiyin Disease (Spleen-Yang Deficiency Syndrome) and other relevant points provides theoretical basis for when to choose treatment, to realize the conversion of basic research achievements, in order to serve for clinical.

课题组完成的国家自然科学基金项目"太阳病（风寒表证）'欲解时'与白介素变化的相关性研究"结果表明：模型动物白介素含量和节律变化与太阳病（风寒表证）"欲解时"密切相关。在此基础上，依据中医脾主运化、为气血生化之源的理论，开展太阴病（脾阳虚证）"欲解时"与cAMP变化的相关性研究，进一步探讨太阴病（脾阳虚证）"欲解时"cAMP表达及节律变化与太阴病发生、发展规律相关性；选择血淀粉酶及血D-木糖浓度，研究太阴病"欲解时"脾的运化功能状态；检测外周血液，探讨太阴病气血生化之变化；通过胃、小肠、胰腺等脏器的形态学观察,研究太阴病（脾阳虚证）的组织病理学变化。从机体能量代谢、消化机能、气血生化变化等方面，阐释太阴病（脾阳虚证）"欲解时"的生理病理学基础。并通过观察理中汤干预后太阴病（脾阳虚证）"欲解时"及其他相关时点cAMP等相关指标的变化，为择时治疗提供理论依据，实现基础研究成果的转化，为临床服务。

《伤寒论》六经病“欲解时”属于时间医学范畴，本课题通过太阴病（脾阳虚证）模型大鼠在“欲解时”及其他时段血浆环磷酸腺苷（cAMP）、环磷酸鸟苷(cGMP)、血清淀粉酶、血D-木糖、外周血等指标变化及相关脏器形态学变化，理中汤干预效果研究，探讨了太阴病（脾阳虚证）“欲解时”的病理生理基础，为全面阐释“欲解时”科学性和客观性提供证据。. 实验研究表明：①高寒地区更易于制备脾阳虚大鼠模型，提示不同地域环境造模条件存在可变性。②检测血浆cAMP、cGMP指标的变化，实验各组均未显示有显著的时间节律性，推测cAMP、cGMP的变化主要反映了太阴病（脾阳虚证）发展中能量代谢的变化，但不具有时间生物学调控意义。③太阴病（脾阳虚证）模型大鼠血清D-木糖酉时、午时总体低于子时；理中汤治疗后，血清D-木糖值药物组血清D-木糖值较模型组升高，尤于子时升高明显。④血清淀粉酶在实验大鼠体内的表达没有明显的时点节律，其含量的增高可能与血清淀粉酶参与水谷精微的转运及大鼠夜间活动大、能量消耗增加有关。⑤正常组，模型组、药物组大鼠Hb、PLT、MPV、PDW变化不明显；正常组，模型组、药物组外周血白细胞数均呈现昼高夜低的节律性变化，同时模型组低于正常组，药物组高于模型组。⑥太阴病（脾阳虚证）模型大鼠小肠黏膜上皮细胞渗出明显，但无明显缺损性病理结构改变；肝细胞肿胀及脂肪空泡，引起肝细胞点状及灶状炎细胞浸润；子时药物组小肠、肝细胞病理恢复情况优于午时药物组。. 本研究各项指标分析，理中汤具有明显的“温阳”、“健脾”功效，可提高脾阳虚大鼠能量代谢水平和免疫功能，从而改善脾阳虚证。因此，能量代谢下降和免疫功能减退是太阴病的病理生理基础。太阴病某些指标存在一定的时间节律，但“欲解时”的变化不显著，其可能的因素为：①四个时间点的监测，不足以发现其变化的规律；②所选择的指标易被大鼠的饮食、活动习惯干扰，或本身不具有时间生物学调控作用。