从功效角度探讨《金匮》“短气，有微饮”同病异治的内涵

发布时间：2018-06-05 17:18

本文选题：同病异治 + 实证研究　；参考：《北京中医药大学》2017年硕士论文

【摘要】：本论文共分三个部分:文献综述、理论研究、实验研究。文献综述部分,通过整理古代医籍中有关"同病异治"的论述以及近年的研究成果,疏理"同病异治"的理论源流,分析"同病异治"的研究进展与不足。理论研究部分,从多个角度对《伤寒杂病论》中"同病异治"的治疗原则进行分析,发现"同病—异证—异方"的"同病异治"的解读并不是"同病异治"的全部内涵,"同病—同证—异方"是有其可能性的,至少是不矛盾的,其理论和临床价值不可被忽略。实验研究部分,以《金匮要略》"夫短气,有微饮,当从小便去之,苓桂术甘汤主之,肾气丸亦主之"为例,从生物学角度对"同病—同证—异方"的"同病异治"解读进行实验验证。实验研究方面,分两个部分逐步验证:第一部分基于气道黏液高分泌大鼠模型的苓桂术甘汤与肾气丸同病异治之作用比较研究目的:观察苓桂术甘汤与肾气丸对气道黏液高分泌模型大鼠通气功能的影响是否有差异。方法:以丙烯醛雾化吸入方式复制气道黏液高分泌大鼠模型,在造模2周后,将大鼠随机分为模型组、苓桂术甘汤组、肾气丸组。第3周开始灌胃相应中药煎液,持续4周。模型组与正常组以等量纯净水灌胃。4周后,检测各组大鼠的肺功能及动脉血气并取肺组织按常规方法HE染色,进行病理观察。结果:肺功能与动脉血气检测结果与正常组比较,模型组大鼠FVC、FEV1、FEV1/FVC下降(P0.05);动脉血pH、PaO2、SaO2下降,PaCO2升高(P0.05)。提示经过丙烯醛雾化后大鼠气道阻力增加,存在气流受限和通气功能障碍。与模型组比较,苓桂术甘汤组、肾气丸组大鼠肺功能和动脉血气均有改善(P0.05)。苓桂术甘汤组与肾气丸组比较,FVC、FEV1、FEV1/FVC、pH、PaO2、SaO2、PaCO2差异不具有统计学意义(P0.05)。提示苓桂术甘汤与肾气丸均可改善气道黏液高分泌模型大鼠的通气功能,且两方作用效果差异不显著。肺组织病理观察正常组大鼠肺组织可见各支气管管壁、肺泡黏膜结构较完整,肺组织有少量炎性细胞,支气管管腔内未见炎性渗出物,充血不明显。模型组大鼠肺组织支气管及肺泡黏膜不完整,杯状细胞和黏液腺肥大、增生,分泌亢进,阻塞支气管。肺泡结构紊乱,肺泡腔扩大、融合。支气管管壁和肺泡有以中性粒细胞为主的大量炎性细胞浸润。苓桂术甘汤组、肾气丸组大鼠支气管壁也有杯状细胞和黏液腺肥大、增生,肺泡腔扩大、破裂、结构紊乱,炎性细胞浸润等,但与模型组相比病变程度较轻。结论:从本实验研究结果来看,苓桂术甘汤与肾气丸均能改善气道黏液高分泌模型大鼠的通气功能,即可"同病异治"。第二部分基于气道黏液高分泌大鼠模型的苓桂术甘汤与肾气丸同病异治之内涵研究目的:探讨苓桂术甘汤与肾气丸改善气道黏液高分泌模型大鼠通气功能的作用机制。方法:造模、给药方法、肺功能检测、动脉血气分析、肺组织HE染色(同第一部分)。分组增设:苓桂术甘汤去苓桂组、肾气丸去苓桂组、苓桂组、氢氯噻嗪组。用代谢笼收集大鼠24h尿液。用全自动分析仪检测各组大鼠尿液中Na+、K+、Cl-浓度。ELISA法检测大鼠尿液中AQP-2浓度。ELISA法检测大鼠血清中PRA、AngⅡ、ALD浓度。结果:肺功能与动脉血气检测结果与正常组比较,模型组大鼠FVC、FEV1、FEV1/FVC下降(P0.05);动脉血pH、PaO2、SaO2下降,PaCO2升高(P0.05)。提示经过丙烯醛雾化后大鼠气道阻力增加,存在气流受限和通气功能障碍。与模型组比较,苓桂术甘汤组、肾气丸组、苓桂组、氢氯噻嗪组大鼠肺功能和动脉血气均有改善(P0.05);苓桂术甘汤去苓桂组、肾气丸去苓桂组大鼠肺功能和动脉血气均有改善(P0.05)。提示各组药物均可改善模型大鼠的通气功能,其中苓桂术甘汤组、肾气丸组、苓桂组、氢氯噻嗪组作用显著。苓桂术甘汤组与肾气丸组比较,FVC、FEV1、FEV1/FVC、pH、PaO2、SaO2、PaCO2差异不具有统计学意义(P0.05)。提示苓桂术甘汤与肾气丸均可改善气道黏液高分泌模型大鼠的通气功能,且两方作用效果差异不显著,即可"同病异治"。与苓桂术甘汤组比较,苓桂术甘汤去苓桂组大鼠通气功能下降(P0.05)。与肾气丸组比较,肾气丸去苓桂组大鼠通气功下降(P0.05)。提示茯苓、桂枝的配伍在苓桂术甘汤与肾气丸改善模型大鼠通气功能上有突出作用。以上检测结果显示,苓桂术甘汤与肾气丸均可改善气道黏液高分泌模型大鼠的通气功能,且两方作用效果差异不显著,即可"同病异治"。当去除茯苓和桂枝后,苓桂术甘汤与肾气丸改善模型大鼠通气功能的作用均明显减弱,而苓桂组改善模型大鼠通气功能的作用又较为突出。因此,苓桂术甘汤与肾气丸均可改善模型大鼠通气功能且作用差异不显著的原因可能是两方中拥有相同的药对——茯苓、桂枝。肺组织病理观察正常组大鼠肺组织可见各支气管管壁、肺泡黏膜结构较完整,肺组织有少量炎性细胞,支气管管腔内未见炎性渗出物,充血不明显。模型组大鼠肺组织支气管及肺泡黏膜不完整,杯状细胞和黏液腺肥大和增生,分泌亢进,阻塞支气管。肺泡结构紊乱,肺泡腔扩大、融合,支气管管壁和肺泡有以中性粒细胞为主的大量炎性细胞浸润。各给药组大鼠支气管杯状细胞化生、黏液腺体增生、黏液分泌亢进,肺泡破裂、融合等皆有减轻,其中苓桂术甘汤组、肾气丸组、苓桂组改善较为明显。大鼠尿量检测结果与正常组比较,模型组大鼠排尿量减少(P0.05)。提示气道黏液高分泌模型大鼠存在尿液潴留。与模型组比较,苓桂术甘汤组、肾气丸组、苓桂组、氢氯噻嗪组大鼠排尿量均增多(P0.05);苓桂术甘汤去苓桂组、肾气丸去苓桂组大鼠排尿量增多(P0.05)。提示各组药物均可改善模型大鼠尿液潴留。其中苓桂术甘汤组、肾气丸组、苓桂组、氢氯噻嗪组作用显著。苓桂术甘汤组与肾气丸组比较,尿量差异不具有统计学意义(P0.05)。提示苓桂术甘汤与肾气丸均可改善模型大鼠尿液潴留,且两方作用差异不显著。与苓桂术甘汤组比较,苓桂术甘汤去苓桂组大鼠排尿量减少(P0.05)。与肾气丸组比较,肾气丸去苓桂组大鼠排尿量减少(P0.05)。提示茯苓、桂枝的配伍在苓桂术甘汤与肾气丸改善模型大鼠尿液潴留上有突出作用。尿液中AQP-2浓度检测结果与正常组比较,模型组大鼠尿液中AQP-2排出量增多(P0.05)。提示气道黏液高分泌模型大鼠肾脏AQP-2表达增加,尿液的生成减少。与模型组比较,苓桂术甘汤组、肾气丸组、苓桂组、氢氯噻嗪组大鼠尿液中AQP-2浓度降低(P0.05);苓桂术甘汤去苓桂组、肾气丸去苓桂组大鼠尿液中AQP-2浓度降低(P0.05)。提示各组药物均可抑制模型大鼠AQP-2表达,其中苓桂术甘汤组、肾气丸组、苓桂组、氢氯噻嗪组作用显著。苓桂术甘汤组与肾气丸组比较,尿液中AQP-2浓度差异不具有统计学意义(P0.05)。提示苓桂术甘汤与肾气丸均可抑制肾脏AQP-2的表达,且两方作用差异不显著。与苓桂术甘汤组比较,苓桂术甘汤去苓桂组大鼠尿液中AQP-2浓度升高(P0.05)。与肾气丸组比较,肾气丸去苓桂组大鼠尿液中AQP-2浓度升高(P0.05)。提示茯苓、桂枝的配伍在苓桂术甘汤与肾气丸抑制肾脏AQP-2的表达上有突出作用。血清中PRA、AngⅡ、ALD浓度检测结果与正常组比较,模型组大鼠血清中PRA、AngⅡ、ALD浓度升高(P0.05)。提示气道黏液高分泌模型大鼠RASS系统激活。与模型组比较,苓桂术甘汤组、苓桂组大鼠血清中PRA、AngⅡ、ALD浓度降低(P0.05);肾气丸组PRA、AngⅡ降低(P0.05),ALD降低(P0.05);苓桂术甘汤去苓桂组、肾气丸去苓桂组、氢氯噻嗪组大鼠血清中PRA、AngⅡ、ALD浓度降低(P0.05)。提示各组药物均可抑制RASS系统激活,其中苓桂术甘汤组、苓桂组作用显著。苓桂术甘汤组与肾气丸组比较,PRA、AngⅡ、ALD浓度差异均不具有统计学意义(P0.05)。提示苓桂术甘汤与肾气丸均可抑制RASS系统激活,且两方作用差异不显著。与苓桂术甘汤组比较,苓桂术甘汤去苓桂组大鼠血清中PRA、AngⅡ、ALD浓度升高(P0.05);与肾气丸组比较,肾气丸去苓桂组大鼠血清中PRA、AngⅡ浓度升高(P0.05),ALD浓度升高(P0.05)。提示茯苓、桂枝的配伍在苓桂术甘汤抑制RASS系统激活上有突出作用。尿液中Na+、K+、Cl-浓度检测结果与正常组比较,模型组大鼠尿液中Na+、Cl-浓度降低、K+浓度升高(P0.05)。提示模型组大鼠尿液重吸收增加。与模型组比较,苓桂术甘汤组、肾气丸组、苓桂组大鼠尿液中Na+、Cl-浓度升高,K+浓度降低(P0.05);苓桂术甘汤去苓桂组、氢氯噻嗪组大鼠尿液中Na+、Cl-浓度升高(P0.05)。K+浓度降低(P0.05);肾气丸去苓桂组大鼠尿液中Na+、Cl-浓度升高,K+浓度降低(P0.05)。提示各组药物均可抑制尿液重吸收,而苓桂术甘汤组、肾气丸组、苓桂组作用更为显著。苓桂术甘汤组与肾气丸组比较,Na+、K+、Cl-浓度差异均不具有统计学意义(P0.05)。提示苓桂术甘汤与肾气丸均可抑制尿液重吸收,且两方作用差异不显著。与苓桂术甘汤组比较,苓桂术甘汤去苓桂组大鼠尿液中Na+、Cl-浓度降低(P0.05),K+浓度升高(P0.05);与肾气丸组比较,肾气丸去苓桂组大鼠尿液中Na+、Cl-浓度降低,K+浓度升高(P0.05)。提示茯苓、桂枝的配伍在肾气丸抑制尿液重吸收上有突出作用。综合分析以上检测结果,气道黏液高分泌模型大鼠尿量明显减少,苓桂术甘汤与肾气丸均可通过调节AQP-2的表达、肾素-血管紧张素-醛固酮系统等途径增加模型大鼠的尿量,且茯苓、桂枝的配伍在此作用中占有突出地位。结论:苓桂术甘汤与肾气丸均可改善气道黏液高分泌模型大鼠的通气功能的原因可能是两方均有促进模型大鼠尿液排泄的作用,即仲景所言"当从小便去之"。
[Abstract]:This paper is divided into three parts: literature review, theoretical research, experimental research and literature review. By sorting out the theories of "disease and hetero treatment" in ancient medical books and research achievements in recent years, the theoretical origin of "same disease and hetero treatment" is ignored. The analysis of the treatment principle of "the same disease and different treatment" in the theory of disease has found that the interpretation of "the same disease and different treatment" is not the whole connotation of "the same disease and different treatment". The "same disease - the same evidence - different prescription" has its possibility, at least not contradictory, its theory and clinical value can not be ignored. There are two parts in the experimental study: the first part is the Gump soup and kidney qi, which is based on the mucus hypersecreting rat model of the airway. Objective: To observe whether there is a difference between the effect of Ling Gui Shu Gan Tang and Shenqi Pill on the ventilation function of the airway mucus hypersecretion model in rats. Methods: the airway mucus hypersecreting rat model was replicated with acrolein atomization inhalation. After 2 weeks, the rats were randomly divided into model group, Gump Decoction group, kidney qi, and kidney qi. After third weeks, the decoction of traditional Chinese medicine was administered for 4 weeks. The model group and the normal group were treated with the same amount of pure water for.4 weeks. The pulmonary function and arterial blood gas of the rats were detected and the lung tissue was stained by the routine method of HE. The results of lung function and arterial blood gas test were compared with the normal group, and the model group was FVC, FEV1, FEV1/FVC decreased (P0.05); arterial blood pH, PaO2, SaO2 decreased, PaCO2 increased (P0.05). It suggested that the airway resistance increased in rats after acrolein atomization, and there was airflow limitation and ventilation dysfunction. Compared with the model group, the lung function and arterial blood gas of the rats in the Luli Gump Decoction group and the kidney qi pill group were improved (P0.05). The difference between FVC, FEV1, FEV1/FVC, pH, PaO2, SaO2, PaCO2 is not statistically significant (P0.05). It is suggested that Gump Tang and Shenqi pills can improve the ventilation function of the airway mucus hypersecretion model rats, and there is no significant difference in the effect between the two parties. The lung tissue has a small number of inflammatory cells, no inflammatory exudation in the bronchial tube and no obvious congestion. The bronchial and alveolar mucous membrane in the lung tissue of the model group is incomplete, the goblet cells and mucous glands are hyperhypertrophic, hyperhyperplastic, obstructed bronchioles, alveolar structure disorder, alveolar cavity enlargement, fusion, bronchial tube wall and alveolus. A large number of inflammatory cells infiltrated by neutrophils. The bronchi and mucous glands of the rats in the Shenqi decoction group and the kidney qi pill group had hypertrophy, hyperplasia, alveolar cavity enlargement, rupture, structural disorder and inflammatory cell infiltration, but compared with the model group, the degree of pathological changes was lighter. Conclusion: from the results of the experimental study, Lilin Gump soup and kidney Qi pill can improve the ventilation function of the airway mucus hypersecretion model rats. The second part is based on the connotation of the connotations of the same disease of the Luli Gump soup and the kidney qi pill based on the airway mucus hypersecreting rat model. Methods: modeling, drug delivery, lung function test, arterial blood gas analysis, HE staining of lung tissue (the same first part). Group adding: Luli Gump decoction, Guangxi group, Shenqi Pill, Luli group, Luli group, hydrochlorothiazide group. The urine of rats was collected by metabolic cage. The urine Na+, K+, Cl- concentration in the urine of rats in each group were detected by.ELISA method. Test the concentration of PRA, Ang II and ALD in rat serum by detecting the concentration of AQP-2 in rat urine. Results: compared with the normal group, the results of lung function and arterial blood gas detection were compared with the normal group. The model group was FVC, FEV1, FEV1/FVC decreased (P0.05), and the arterial blood pH, PaO2, SaO2 decreased and increased. Compared with the model group, the lung function and arterial blood gas of the rats in the Luli Gump soup group, the kidney qi pill group, the Luli group and the hydrochlorothiazide group were improved (P0.05); the lung function and arterial blood gas of the rats in the Luli Gump Decoction and the Shenqi Pill to the Luli group were improved (P0.05). The ventilation function of rats in the group of Luli Gump soup, kidney qi pill group, Ling Gui group and hydrochlorothiazide group was significant. The difference of FVC, FEV1, FEV1/FVC, pH, PaO2, SaO2, PaCO2 was not statistically significant (P0.05) in the group of Luli Gump Decoction and kidney qi pill group. There was no significant difference in the effect of two parties. Compared with the Gump Decoction group of Luli Gump decoction, the ventilation function of the rats was decreased (P0.05). Compared with the kidney qi pill group, the Qi Qi pill of Shenqi Pill was decreased (P0.05). The results showed that the Luli Gump Decoction and Shenqi Pill could improve the ventilation function of the airway mucus hypersecretion model rats, and the difference of the effect of the two parties was not significant, which could be "the same disease and different treatment". After the removal of Poria and cinnamon branches, the effect of Luli Gump soup and kidney qi pills on the ventilation function of the model rats was improved. The effect of Luli Gump Decoction and kidney qi pill can improve the ventilation function of the model rats and the difference is not significant, which may be the same drug pair in the two parties - Poria cocos, cinnamon branch. Lung tissue pathology observation of lung tissue in the normal group of rats can be seen in the lung tissue. Tracheal tube wall, alveolar mucous membrane structure is more complete, lung tissue has a small number of inflammatory cells, no inflammatory exudation in the bronchial tube, no obvious congestion. Model group rats lung tissue bronchus and alveolar mucous membrane incomplete, goblet cells and mucous glands hypertrophy and hyperplasia, hypersecretion, obstruction of bronchi, alveolar structure disorder, alveolar cavity enlargement, fusion, The bronchial tube wall and the alveoli were infiltrated with a large number of inflammatory cells based on neutrophils. All the rats in the group were relieved of the goblet cell metaplasia, mucous gland hyperplasia, mucus secretion, alveolar rupture, and fusion, and the improvement of the Luli Gump soup group, the kidney qi pill group and the Lili group was more obvious. Compared with the model group, the urine retention in the model rats was reduced (P0.05). Compared with the model group, the urine volume of the rats in the Luli Gump soup group, the kidney qi pill group, the Lili group and the hydrochlorothiazide group increased (P0.05), and the amount of urination in the Luli Gump Decoction and the Shenqi Pill was increased (P0.05). Each group of drugs can improve the retention of urine in the model rats. In the group of Luli Gump decoction, the kidney qi pill group, the Luli group and the hydrochlorothiazide group, the difference of urine volume is not statistically significant (P0.05). The results suggest that the urine retention of the model rats can be improved by the Luli Gump Decoction and the kidney qi pill, and the effect of the two party is poor. Compared with the Gump Decoction group of Luli operation Gump Decoction group, the urine volume of the rats in the Gump Decoction of Gump decoction was reduced (P0.05). Compared with the kidney qi pill group, the urine volume of the kidney qi pill was reduced (P0.05). It suggested that the compatibility of the Poria cocos and cinnamon branch had a prominent effect on the urine retention of the model rats. The urine AQP-2 concentration was detected. Compared with the normal group, the amount of AQP-2 excretion in the urine of the model rats increased (P0.05). It was suggested that the expression of AQP-2 in the kidney of the airway mucus hypersecretion model increased and the formation of urine decreased. Compared with the model group, the concentration of AQP-2 in the urine of the rats in the Luli Gump soup group, the kidney qi pill group, the Lili group and the hydrochlorothiazide group decreased (P0.05). The concentration of AQP-2 in the urine of rats in Luling group of Luli group was reduced (P0.05). It was suggested that all the drugs could inhibit the expression of AQP-2 in the model rats, including the group of Luli Gump soup, the kidney qi pill group, the Luli group and the hydrochlorothiazide group. The difference of AQP-2 concentration in the urine of Luli Gump Decoction group and the kidney qi pill group was not statistically significant (P0.05). It is suggested that the expression of AQP-2 in kidney can be inhibited by Ling Gui Shu Gan Tang and Shenqi Pill, and the difference between the two parties is not significant. Compared with the Gump Decoction group of Luli Gump decoction, the concentration of AQP-2 in the urine of the rats in the Gump Decoction of Gump decoction is increased (P0.05). Compared with the Shenqi Pill group, the concentration of AQP-2 in the urine of the rats in the rats of the kidney qi pill is higher (P0.05). Compared with the normal group, the serum concentrations of PRA, Ang II, and ALD were compared with the normal group, and the serum concentration of PRA, Ang II and ALD increased (P0.05) in the model group. The results showed that the RASS system in the model rats was activated by the model group. The comparison between the model group and the model group, Lili Gump soup group, Lili and laurel, was compared with the model group. Group PRA, Ang II, ALD concentration decreased (P0.05), kidney qi pill group PRA, Ang II reduction (P0.05), ALD reduction (P0.05); Luli Gump decoction, Guangxi group, Shenqi Pill to Luli group, hydrochlorothiazide group rats serum PRA, Ang II, ALD concentration decreased. Compared with the group of Shenqi Pill, PRA, Ang II and ALD concentration were not statistically significant (P0.05). It was suggested that Gump Tang and Shenqi pills could inhibit the activation of RASS system, and the difference between the two parties was not significant. Compared with the Gump Decoction group of Luli operation Gan Tang Group, the serum of PRA, Ang II and ALD concentration in the Gump Decoction of Gump Decoction of Gump Decoction were PRA, Ang II, ALD concentration. Du Shenggao (P0.05); compared with the Shenqi Pill group, the concentration of PRA, Ang II in the serum of the rats in the kidney qi pill and the concentration of Ang II increased (P0.05), and the concentration of ALD increased (P0.05). It suggested that the compatibility of cassia twig was prominent in the inhibition of RASS system activation in the Luli Gump soup. The results of the urine Na+, K+, Cl- concentration were compared with the normal group, and the urine of the model rats was Na+, The concentration of Cl- decreased and the concentration of K+ increased (P0.05). It was suggested that the urine reabsorption of rats in the model group increased. Compared with the model group, the urine of Luli Gump soup group, kidney qi pill group and Luli group increased the urine Na+, Cl- concentration and K+ concentration decreased (P0.05); the concentration of Na+ in urine in the urine of the hydrochlorothiazide group and the.K+ concentration (P0.05) decreased (P0.05).K+ (P) (P) (P0.05).K+ concentration (P) was reduced (P) 0.05): the concentration of Na+, Cl- and K+ in the urine of Shenqi Pill were increased and the concentration of K+ decreased (P0.05). It was suggested that the drug can inhibit the reabsorption of urine, and the effect of Luli Gump Decoction group, kidney qi pill group and Luli group was more significant. The difference of Na +, K+ and Cl- concentration was not statistically significant (P0.05) in the Luli Gump Decoction group and the kidney qi pill group (P0.05). GUI Zhu Gan Tang and Shenqi Pill can inhibit the reabsorption of urine, and the difference between the two parties is not significant. Compared with the Luli Gump Decoction group, the concentration of Na+, Cl- in the urine of Gump Decoction of Luli Gump Decoction (P0.05) and the concentration of K+ increased (P0.05), and the concentration of Na+, Cl- in the urine of Shenqi Pill and the concentration of Cl- in the rats of the kidney qi pill was lower, and the concentration of K+ increased (P0.0). 5) suggest that Poria, cinnamon branch has a prominent role in the inhibition of urine reabsorption by Shenqi Pill. Comprehensive analysis of the results of the above detection results, the urine volume of the airway mucus hypersecretion model rats significantly reduced, Luli Gump soup and kidney qi pills can be regulated by the expression of AQP-2, renin angiotensin aldosterone system and other ways to increase the urine of model rats In addition, the combination of tuckahoe and cinnamon branch plays a prominent role in this role. Conclusion: the reason that Luli Gump Decoction and kidney qi pill can improve the ventilation function of the rat model of airway mucus hypersecretion may be that the two parties have the effect of promoting the urine excretion of model rats, that is, Zhong Jing said "go from the urine."
【学位授予单位】：北京中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R222.3

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