补骨脂盐炙“入肾”机理研究

Traditional Chinese medicine theory is one of the key issues in the development of Traditional Chinese Medicine. Although the fact that Stir-frying with salt-water could make Malaytea Scurfpea enter the kidney and enhance the the function of Reinforcing Kidney for Relieving Diarrhea has been accepted by medical scientist, but the mechanism is indefinite. This project adopts Malaytea Scurfpea as the model drug, theory of ‘with salt entering the kidney' as the breakthrough point, according to Chinese Medical Theory of ‘kidney governing bones, urine and stool' to propose the hypothesis: After stir-frying with salt-water, ‘entering the kidney' function of Malaytea Scurfpea reflects on the enhance of ‘stronger bones' and ‘checking diarrhea', which is attributed to the salt and (or) heat who affect absorption and kidney-correlated distribution of drugs. Enterorrhea and osteoporosis model will be adopted to verify that stir-frying with salt-water could make Malaytea Scurfpea enter the kidney; Pharmacokinetic methods will be used to study the absorption and kidney-correlated distribution of three kinds of representative components, accordingly to clarify the path of stir-frying with salt-watered Malaytea Scurfpea enter the kidney, and find its correlation with chemistry and pharmacodynamics. Different processed products of Malaytea Scurfpea will be prepared, comparing the absorption and distribution of their representative components could help us to find the influential factors. The purpose is to reveal the mechanism of stir-frying with salt-watered Malaytea Scurfpea enter the kidney and strengthen the function of Reinforcing Kidney for Relieving Diarrhea, which could provide a scientific basis for the technological improvement of Malaytea Scurfpea, and the theory of ‘with salt entering the kidney’.

中药炮制理论是中医药研究与发展的关键问题之一。补骨脂盐炙入肾并增强补肾止泻作用为历代医家所认可，但其入肾增效机理尚不明确。本项目以“入盐走肾”理论为切入点，根据“肾主骨，司二便”的中医理论，提出研究假说：补骨脂盐炙后“入肾”作用体现在增强“强骨”和（或）“止泻”方面，并通过盐和（或）热因素改变吸收和（或）“与肾相关脏器”分布情况得以实现。采用泄泻和骨代谢异常动物模型，多指标确证补骨脂盐炙“入肾”作用；采用药代动力学方法，研究补骨脂三类代表性成分体内吸收和在“与肾相关脏器”分布情况，阐述其盐炙品“入肾”的途径，并采用“多成分PK-PD模型”分析其与化学、药效学研究的相关性；制备补骨脂不同模拟炮制品，比较代表成分吸收分布情况，寻找改变吸收分布的因素。本研究试图揭示补骨脂盐炙后引药入肾，增强补肾止泻作用的内涵和机理，为补骨脂盐炙工艺改进提供支撑，也为“入盐走肾”炮制理论提供研究依据。

中药炮制理论是中医药研究与发展的关键问题之一。补骨脂盐炙入肾并增强补肾止泻作用为历代医家所认可，但其入肾增效机理尚不明确。本项目系统整理了“入盐走肾”炮制理论的现状，并提出了在确证辅料盐品种及用量的基础上，采用“多指标化学成分-多模型药理指标-中医‘肾’药物代谢动力学”模式，综合分析盐炙过程中的“盐效应”和“热效应”，并进行相关性分析，系统解释盐炙“走肾”炮制理论的思路。以补骨脂为切入点，研究了盐炙对补骨脂化学成分的影响，发现补骨脂盐炙前后香豆素类、黄酮类、酚萜类成分变化规律，证明“热效应”影响其化学成分绝对含量，“盐效应”影响其水煎液中化学成分相对含量。本项目探讨了盐炙前后补骨脂在骨代谢异常及泄泻模型的药效学区别，发现补骨脂盐炙后，在促进骨骼生长及止泻方面，较生品有增强趋势（不显著），初步证明补骨脂盐炙后有“入肾”的作用。药代动力学研究方面，补骨脂盐炙之后，促进了补骨脂素、异补骨脂查尔酮、补骨脂二氢黄酮甲醚、corylifol A成分的吸收。代谢组学研究方面，盐补骨脂使动物机体整体的代谢水平更亢进，代谢物水平也更高，助阳作用更强；盐补骨脂可降低其在肾脏和心血管系统方面的毒副作用，这与萜酚类成分密切相关；补骨脂盐炙前后在抑制成骨细胞凋亡等方面具有一致性，说明盐炙过程虽然对补骨脂某些化学成分的种类和含量有一定程度的改变，但有些特性得以保留。本项目的研究，初步揭示了补骨脂盐炙后引药入肾，增强其补肾助阳，缓和燥性的炮制机理，为其他盐炙药物的机理研究提供借鉴和参考。