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韭菜子盐炙前后温补肾阳的机理研究
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摘要
韭菜子为百合科植物韭菜Alliium tuberosum Rottl的干燥成熟种子;辛、甘、温,归肝、肾经;功能为温补肝肾,壮阳固精;用于阳痿遗精,腰膝酸痛,遗尿尿频,白浊带下。《中国药典》“炮制”项下分列“韭菜子”和“盐韭菜子”两个饮片品种,其中“韭菜子”由韭菜子“除去杂质”而来,“盐韭菜子”由净韭菜子“照盐水炙法炒干”而成。韭菜子生品较少应用,临床多用盐炙品,盐炙后可引药下行,增强补肾固精作用。
     目的
     本文选用韭菜子为研究对象,基于古今对其炮制方法存在较大差异的历史背景,以不同炮制方法对韭菜子“温补肾阳”作用的影响为切入点,拟初步阐明盐韭菜子“温补肾阳”作用的机理和物质基础,进而解释韭菜子“盐制入肾”理论的科学内涵,并在阐明这一功效药效物质的基础上,初步研究韭菜子盐炙工艺和盐炙品质量标准。
     方法
     采用文献学、药理学和化学相结合的手段开展韭菜子盐炙的炮制学研究。
     1采用文献学方法,整理中药韭菜子的炮制历史沿革,搞清中药韭菜子炮制的历史情况和现代应用现状。
     2采用药理学方法,开展韭菜子四种炮制品温补肾阳功效的药效学对比研究,并探讨其可能的作用机制,认识韭菜子不同炮制方法对温补肾阳作用的影响。
     3温补肾阳作用机理研究:在肾阳虚模型基础上,进行小鼠交配实验、大鼠生殖器官重量、睾丸组织学观察;并测定小鼠血浆促肾上腺皮质激素含量和血清睾酮含量。
     4采用化学方法,以药效为导向,筛选盐韭菜子温补肾阳作用的有效部位,并用指纹图谱技术控制有效浸出物的质量。
     5在上述研究的基础上,开展韭菜子盐炙工艺和盐炙饮片质量标准的初步研究。
     结果
     1韭菜子具有降低肾阳虚小鼠肾上腺中VitC含量和延长肾阳虚小鼠耐寒死亡时间的作用。韭菜子经盐炙后其降低肾阳虚小鼠肾上腺中VitC含量作用进一步增强,生韭菜子在成人日服剂量100倍时起效,而盐韭菜子在成人日服剂量60倍时起效,辅料食盐和韭菜子具协同增效作用。韭菜子经酒炙后延长肾阳虚小鼠耐寒死亡时间的作用进一步增强,生韭菜子在成人日服剂量140倍时起效,而酒韭菜子在成人日服剂量80倍时起效,辅料黄酒和韭菜子具协同增效作用。
     2韭菜子生品和盐炙品均可显著提高肾阳虚小鼠血浆促肾上腺皮质激素和血清睾酮的含量,并能提高肾阳虚小鼠交配能力,其中盐炙品提高血浆促肾上腺皮质激素含量的作用强于生品。韭菜子生品和盐炙品均可显著提高肾阳虚大鼠睾丸脏重系数,并能提高各级生精细胞数量,其中盐炙品提高初级精母细胞一次级精母细胞和精子细胞数量的作用强于生品。
     3“醇水双提-正丁醇浸出物+食盐”是盐韭菜子“温补肾阳”作用的有效部位;采用HPLC技术对该部位建立了指纹图谱。
     4初步建立的韭菜子盐炙工艺是:每100kg药材加入2kg食盐,同时加入55kg水,常温润制6小时后置于150℃炒置容器内,以40次/min的翻炒频率炒制15分钟。
     结论
     韭菜子具有一定温补肾阳的作用,不同炮制方法对其疗效有所影响,盐炙后能进一步增强肾上腺皮质功能,酒炙后能进一步提高耐寒能力,炒制后能利于药材粉碎促进成分溶出,说明古人采用炒制的炮制方法并有“酒糊为丸,盐汤送服”用药要求的科学合理性,也为现代韭菜子采用盐炙法找到了科学依据。辅料食盐和黄酒对韭菜子温补肾阳作用具协同增效作用。“醇水双提-正丁醇浸出物+食盐”是盐韭菜子“温补肾阳”作用的有效部位。盐韭菜子温补肾阳的机理在于增加促肾上腺皮质激素的分泌而促进肾上腺皮质功能;提高交配能力、睾丸脏重系数和曲细精管内各级生精细胞数量,该作用可能与促进睾酮的分泌和释放有关。
     创新点
     1初步阐明盐炙、酒炙和炒制三种炮制方法对韭菜子温补肾阳作用的影响。
     2研究食盐和黄酒两种辅料与韭菜子温补肾阳作用的相关性,初步阐明两种辅料与韭菜子温补肾阳作用的协同增效关系,为中药“盐炙入肾”和用酒“以热助热”的传统炮制理论找到了一定的科学依据。3初步阐明盐韭菜子温补肾阳作用的物质基础和机制。
Semen Allii Tuberosi is the dry ripe seed of Alliium tuberosum Rottl, pungent and sweet in flavour, warm, acting on the liver channel and the kidney channel. Its function is warming and tonifing the liver and kidney, invigorating Yang and control nocturnal emission, usually being used to treat impotence and seminal emission, ache of waist and knees, enuresis, frequent micturition, cloudy urine, morbid leucorrhea drolling and emissions, premature ejaculation. There are two kinds of processed forms in'Pharmacopoeia of the People's Republic of China', which are'The Crude Seed Allii Tuberosi (CSAT)'and'The Stir-heated Seed Allii Tuberosi (SSAT)', CSAT is processed by excluding impurity, and SSAT is stir-heating the CSAT with salt solution.
     Objective
     This paper selects Semen Allii Tuberosi as the research object, bases on the background of large differences in its processed ways in history, takes the different processed products'effect of Warmly Invigorate Kidney-Yang as the breakthrough point, intends to preliminary clarify SSAT mechanism and material basis of the Warmly Invigorate Kidney-Yang effect, further interpreting the scientific connotation of the theory for "The stir-heated drug with salt solution acts on kidney", study the stir-heated drug with salt procesed of Semen Allii Tuberosi, and study the product quality standard of SSAT.
     Methods
     The methods used in the research of the scientific connotation of the theory for the stir-heated CSAT with salt solution are philological, pharmacological and chemical means.
     1. Systemically arrange the documents about the processing methods of the past and follow up the modern report timely by philological means in order to recognize the history and actuality of CSAT.
     2. Using pharmacological methods, conduct CSAT four processed products effect of Warmly Invigorate Kidney-Yang pharmacodynamics contrast studing, and also discuss the possible mechanism, recognize the CSAT effect of Warmly Invigorate Kidney-Yang.
     3. Warmly Invigorate Kidney-Yang mechanism research:using Kidney-Yang deficiency mouse model as the study object, the mechanism was investigated through the mouse mating reproductive organs weight testicular tissue observations; And the determination in plasma corticotropin hormone levels and serum testosterone levels.
     4. Take efficacy as the guidance by using chemical method, the active fraction with Warmly Invigorate Kidney-Yang effect of SSAT was screened, and the effectively extract quality was be controlled by fingerprint technology.
     5. On the basis of the study, study stir-baking with salt solution process of CSAT and preliminary study the quality standard of SSAT.
     Results
     1. CSAT has function of lowering vitamin C content in adrenaline of Kidney-Yang deficiency mice, and extending time of death of Kidney-Yang deficiency mice in hardy. CSAT through stir-heating with salt solution the function in lowering content of vitamin C in adrenal get further strengthen, with 100 times adult dosage, CSAT play the action, and SSAT play the action with 60 times adult dosage, and the salt played a synergistic role. CSAT through stir-heating with wine solution the function in extending time of death of Kidney-Yang deficiency mice in hardy get further strengthen, with 140 times adult dosage, CSAT play the action, and the product of stir-heating the CSAT with wine solution play the action with 80 times adult dosage, and the rice wine also played a synergistic role.
     2. CSAT and SSAT could also significantly increase the plasma ACTH and serum testosterone concentration of Kidney-Yang deficiency mice, could also increase mating ability of Kidney-Yang deficiency mice, among them SSAT has better action than CSAT in increasing the plasma ACTH concentration. CSAT and SSAT could also significantly increase the weight of testicle of Kidney-Yang deficiency rat, and could improve the number of sperm cells at birth, among them SSAT has better action than CSAT in increasing the number of primary pure mother cells-subprime pure mother cells and sperm cells.
     3. "Alcohol water double extract-n-butanol extract+salt" is active fraction with Warmly Invigorate Kidney-Yang effect of SSAT; Fingerprint of active fraction was established by HPLC technology.
     4. Preliminary established process of stir-baking with salt solution for CSAT is: Every 100kg crude drugs add 2kg salt and 55kg water, moisten in the room temperature for 6 hours and then stir-fry at 150℃with 40 times/min of stirring frequency for 15 minutes.
     Conclusions
     CSAT has certain effect of Warmly Invigorate Kidney-Yang, different processing methods of herbs have influence to their efficacy, stir-baking with salt solution can further enhance the adrenocortical function, stir-baking with wine solution can further improve chillness-tolerance ability, stir-frying solution can benefit crude drugs crushing and promote medicinal ingredients dissolving, the scientific rationality the ancients ways which stir-frying solution for the CSAT and "wine paste for pills and salt soup send service" was proved, and also found the scientific basis for SSAT used in modern. The salt and rice wine both played a synergistic role in effect of Warmly Invigorate Kidney-Yang at different parts. "Alcohol water double extract-n-butanol extract+salt" is active fraction with Warmly Invigorate Kidney-Yang effect of SSAT. The mechanism with Warmly Invigorate Kidney-Yang effect of SSAT lies in increasing corticotropin hormone secretion to enhance adrenocortical function, and its improving the mating ability, testicular weight and various raw number of all kinds of sperm cells may be related with increasing testosterone hormone secretion.
     Innovations
     1. Preliminary clarified the influence to Warmly Invigorate Kidney-Yang effect of CSAT by three kinds of processing method which are stir-baking with salt solution stir-baking with wine solution and stir-frying solution.
     2. Elucidating the synergistic actions of CSAT and salt or rice wine for Warmly Invigorate Kidney-Yang effect, such can certify the TCM theory about "the stir-heated drug with salt solution acts on kidney"
     3. Elucidating the active components and mechanisms for Warmly Invigorate Kidney-Yang effect of SSAT.
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