【作者】 张诏；

【导师】 陶汉华；

【作者基本信息】 山东中医药大学 ， 中医临床基础， 2010， 博士

【摘要】 本论文首先对“肾主生殖”与“肾主水”这两大生理功能等内容从文献角度进行系统阐释和论述；对一直存在较多争议的关于“肾精”、“肾气”、“肾阴”、“肾阳”等基本概念,从其产生历史渊源角度进行探讨；又着重对补肾名方肾气丸、右归丸的功用及配伍规律做出了辨析,对两方功用、主治证候、古今临床应用等进行比较,从而提出“肾气丸补肾气为主,主要侧重于恢复肾主水之功能；右归丸温补肾阳为主,主要侧重于恢复肾主藏精、主生殖功能”的假说。对此进行了动物实验研究,以期对中医理论中“肾主生殖”、“肾主水”有更为深入的认识,并对补肾治法的机理进行初步比较。目的：在充分参考现有“肾阳虚”模型优劣基础上,采用“劳倦过度、房室不节”传统病因造模,与“庆大霉素”病理造模相结合的造模方法,建立“劳倦过度、房室不节加庆大霉素”的肾阳虚大鼠模型,利用该模型,主要从生殖机能及肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system, RAAS)入手,观察肾气丸、右归丸对肾阳虚大鼠的生殖机能及RAAS激素的影响,从而揭示两方在补肾机理方面的差异。方法：通过强迫大鼠游泳造成劳倦过度,并以College效应诱导房室不节,同时加用加注射庆大霉素造成肾阳虚模型；应用肾气丸、右归丸混悬液灌胃以分别进行药物干预；主要采用酶联免疫分析、细胞组织化学等技术,对各实验组大鼠精子质量,血清性激素睾酮(testosterone, T)、卵泡刺激素(follicle-stimulating hormone, FSH)、黄体生成素(lymphatic system, LH)及肾素、血管紧张素Ⅱ(angiotensinⅡ, AngⅡ)、醛固酮(aldosterone, ALD)等进行测定。结果：1.通过对大鼠一般情况的观察,表明本实验采取造模方法可以成功复制出肾阳虚大鼠模型。肾阳虚大鼠睾丸重量下降、精子数量减少、存活率、精子活动率低,畸形率高；而肾气丸、右归丸可提高大鼠睾丸重量、增加精子数量、提高存活率、增强精子活动率,降低畸形率。2.造模过程对肾素无明显影响,但可致AngⅡ、ALD水平升高,肾气丸、右归丸干预对升高的AngⅡ无明显影响,肾气丸对ALD有降低作用,右归丸可使高ALD水平有降低趋势,但无统计学意义。3.造模过程可使T、FSH、LH水平下降,肾气丸、右归丸对T、FSH、LH水平均有不同程度恢复作用,但右归丸效果略优于肾气丸。结论：“劳倦过度、房室不节加庆大霉素”造模方法可成功复制出大鼠肾阳虚模型。肾阳虚大鼠出现了生精功能低下及部分RAAS激素的紊乱,肾气丸、右归丸可改善肾阳虚模型大鼠生精功能,且右归丸略优于肾气丸。提示右归丸对“肾主生殖”的生理功能恢复略优于肾气丸。肾气丸对RAAS中的ALD水平有明显影响,提示肾气丸对“肾主水”的生理功能恢复略优于右归丸。更多还原

【Abstract】 This paper first systematically explains the two physiological functions of "the kidney controlling reproduction" and "the kidney controlling water metabolism" etc on the angle from literature. We discuss the fundamental conceptions of "kidney-JING" "kidney-QI" "kidney-YIN""kidney-YANG" which exist lots of controversy on the angle from historical origin.We also take it as emphasis that compare Kidney-qi Bolus with Yougui Bolus which both of are famous formula of tonifying kidney about effects and formulation,and contrast them on effects,indications,historic and contemporary herbal use.According to the analysis as above,we propose a hypothesis:Kidney-qi Bolus, whose target axis is chiefly located in hypothalamus-pituitary-kidney (HPK), is mainly used to recover the kidney controlling water metabolism. In contrast, Yougui Bolus, whose target axis is chiefly located in hypothalamus-pituitary-didymus(HPD), is mainly used to recover the function of the kidney storing the essence and controlling reproduction.We carried out animal experiments research,in order to obtain the further acknowledge of "the kidney controlling reproduction" and "the kidney controlling water metabolism"of traditional Chinese medicine,at the same time we tried to reveal preliminary mechanisms of tonifying kidney.Objective:Referring to available models of kidney-Yang deficiency syndrome, induced by " fatigue excess, intemperate sexual intercourse " at the point of view of etiology and "Cidomycin" at the point of view of pathology,we we will make a model of rats of renal deficiency.This paper aims to reveal different mechanisms of tonifying kidney between Kidney-qi Bolus and Yougui Bolus targeting at function of reproduction and renin-angiotensin-aldosterone system. Methods:It is induced by forced to swim everyday, College effects and Cidomycin to establish the rat model with "fatigue excess, intemperate sexual intercourse" of kidney-Yang deficiency syndrome. The suspension of Kidney-qi Bolus and Yougui Bolus by gavage is used to treat it.Adoptting technology of enzyme immunoassay and cellular tissue chemistry, we determine indicators in each group mouse,including sperm quality,testosterone, follicle-stimulating hormone,lymphatic system,renin,angiotensin II and aldosterone.etc.Results:1.The observation of change of the general condition showed that the mouse model of kidney-Yang deficiency syndrome caused by overfatigue and sexual overstrain was established.In the model group with kidney-Yang deficiency syndrome,the weight of testis,the amount and motility of sperm were lower than those in the control group,which reduced survival rate and increased deformity rate. Both Kidney-qi Bolus and Yougui Bolus resulted in increasing weight of testis,the amount and motility of sperm,so as to the higher survival rate and lower deformity rate.2.The process of establishing model had no significant effect on renin,but raised the level of Ang II and ALD.After the treat of Kidney-qi Bolus and Yougui Bolus,the higher level of Ang II didn’t change.It suggested that Kidney-qi Bolus may decrease the level of ALD.Although the ALD of the test group with Yougui Bolus indicated declining tendency,it made no sense in Statistics.3.During the process of establishing model,the level of T,FSH and LH had declined.Both the treat of Kidney-qi Bolus and Yougui Bolus raised the three indicators at different degrees,but the effect of the latter was better.Conclusion:The mouse model of kidney-Yang deficiency syndrome is successfully established by "overfatigue, sexual overstrain and Gentamycin",which manifests spermatogenesis failure and part of RAAS hormone disorder. With Kidney-nourishing therapy by Kidney-qi Bolus and Yougui Bolus, above-mentioned function has been improved,and the latter’s effect is better.This paper reveals that the recovery to the function of "the kidney controlling reproduction" of Yougui Bolus is slightly better than that of Kidney-qi Bolus.Meanwhile,that Kidney-qi Bolus makes significant influence on the level of ALD in RAAS suggests its effect on "the kidney controlling water metabolism" is better to a certain extent.更多还原