从作用环节角度探讨《金匮》“短气，有微饮”同病异治的内涵
发布时间：2018-07-17 00:18
【摘要】：本论文从三个方面进行论述:文献综述、理论研究、实验研究。文献综述方面:苓桂术甘汤和肾气丸均见于《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。"类似原文被视为《金匮》"同病异治"的典范。后世常将苓桂术甘汤和肾气丸用于治疗心系疾病。在临床应用方面多是分别研究苓桂术甘汤或肾气丸对慢性心力衰竭、高血压等疾病的治疗作用;在实验研究方面,多是从RAAS系统、炎症因子等角度分别探讨两方对心系疾病起效的作用机制。苓桂术甘汤和肾气丸在防治心系疾病方面有较丰富的临床实践及较扎实的实验研究基础,均能改善"短气,微饮",然《金匮》"同病异治"内涵的研究尚有不足。理论研究方面:①通过分析《黄帝内经》、《金匮要略》中有关"同病异治"的论述和历代医家对原文的解读,及近年来有关"同病异治"的研究成果发现,基于"同病异证异治"的"同病异治"内涵是不全面的,"同病同证异治"是可能存在的,但对"同病同证异治"的实证研究尚不完善。②现代医家从饮邪角度论治心衰取得了很好的疗效,故本实验选取心衰为"短气,微饮"的代表模型。实验研究方面:本论文选取心衰模型为"短气,微饮"代表性模型,开展"同病异治"内涵的实证研究。主要分两部分进行:第一部分基于慢性心衰大鼠模型的苓桂术甘汤和肾气丸"同病异治"之作用比较研究目的:观察苓桂术甘汤和肾气丸对慢性心衰模型大鼠的干预作用是否有差异。方法:取30只健康SD大鼠,利用腹主动脉缩窄法建立慢性心衰大鼠模型,另取10只行假手术。2周后将模型大鼠随机分为①模型组;②苓桂术甘汤组;③肾气丸组,并开始给予中药灌胃,持续4周,模型组与假手术组以纯净水灌胃,各给药组灌胃相应中药。4周后,检测各组大鼠的肺功能、动脉血气。结果:肺功能与血气分析检测结果与假手术组比较,模型组大鼠FVC、FEV1/FVC均降低(P0.05),动脉血pH、Pa02、SO2均降低(P0.05),PaCO2升高(P0.05)。提示模型大鼠存在心功能障碍。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)。苓桂术甘汤组和肾气丸组大鼠肺功能和动脉血气比较,差异不显著(P0.05)。提示苓桂术甘汤与肾气丸均可改善慢性心衰大鼠的心功能,即能改善"短气"。且两方作用效果差异不显著。结论:苓桂术甘汤和肾气丸均可改善慢性心衰模型大鼠的心功能,且两方效果差异不显著,即"同病-同病-异治"的解读是可能存在的。第二部分基于慢性心衰大鼠模型的苓桂术甘汤和肾气丸"同病异治"之内涵研究目的:从作用环节角度探讨苓桂术甘汤和肾气丸改善慢性心衰的机制,为"同病异治"内涵研究提供实证依据。方法:模型建立、给药(同第一部分);实验随机分为①肾气丸组;②苓桂术甘汤组;③模型组:④假手术组。检测肺功能、动脉血气、血流动力学参数;心肌病理(HE染色)观察;用代谢笼收集大鼠24h大鼠尿量;用全自动分析仪检测各组大鼠尿液中Na+、K+、Cl-浓度;ELISA法检测尿液中AQP2浓度;ELISA法检测血清中PRA、AngⅡ、ALD 浓度、炎症因子(IL-6、IL-10、IL-18、IL-1β)浓度、CRP 浓度。结果:肺功能与血气分析检测结果与假手术组比较,模型组大鼠FVC、FEV1/FVC均降低(P0.05),动脉血pH、Pa02、Sa02均降低(P0.05),PaC02升高(P0.05)。提示模型大鼠存在心功能障碍,即存在"短气"。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)。提示上述两方均可改善慢性心衰大鼠的心功能。苓桂术甘汤组和肾气丸组大鼠肺功能和动脉血气比较(P0.05)。提示两方作用效果差异不显著,两方均能改善"短气",即可"同病异治"。尿量、尿液中Na+、K+、Cl-浓度、AQP2浓度检测结果与假手术组比较,模型组大鼠尿量减少(P0.05),尿Na+、Cl-浓度降低(P0.05),K+浓度明显升高(P0.05),尿中AQP2浓度升高(P0.05),提示模型大鼠存在水液潴留。与模型组比较,苓桂术甘汤组、肾气丸组大鼠尿量增多(P0.05),苓桂术甘汤组、肾气丸组大鼠Na+、Cl-浓度明显升高(P0.05),K+浓度明显降低(P0.05),肾气丸组大鼠尿中AQP2浓度降低(P0.05),提示上述两方均有改善模型大鼠水液潴留的作用。苓桂术甘汤组与肾气丸组大鼠尿中离子比较,差异不具有统计学意义(P0.05),提示苓桂术甘汤和肾气丸对模型大鼠水液潴留作用差异不显著。血清中PRA、AngⅡ、ALD浓度检测结果与假手术组比较:模型组大鼠动脉血PRA、AngⅡ、ALD含量均升高(P0.05),提示心衰模型大鼠RAAS系统激活。与模型组比较:苓桂术甘汤组大鼠、肾气丸组大鼠组大鼠PRA、ALD均降低(P0.05),AngⅡ降低不明显(P0.05),提示上述两方均有降低PRA和ALD生成,抑制RAAS系统激活作用。与苓桂术甘汤组比较,肾气丸组大鼠ALD明显降低(P0.05)。提示两方均能抑制ALD生成从而抑制RAAS系统激活这一环节,但肾气丸作用显著。血清中炎症因子(IL-6、IL-10、IL-18、IL-1β)、CRP浓度检测结果与假手术组比较:模型组大鼠血清中IL-6、IL-18、IL-10、TNF-α、IL-1β、CRP均升高(P0.05),提示心衰模型大鼠炎症因子激活。与模型组比较:苓桂术甘汤组大鼠血清中IL-6、IL-18、IL-10、IL-1β浓度均降低(P0.05),肾气丸组大鼠血清中IL-6、IL-10、IL-1β浓度降低(P0.05)。与苓桂术甘汤组比较,肾气丸组大鼠IL-10、IL-18浓度升高(P0.05)。提示苓桂术甘汤明显作用于降低血清中IL-10、IL-18浓度这一环节,从而抑制炎症反应。心肌组织病理观察假手术组:心肌细胞大小、形态正常,心肌纤维排列整齐。模型组心肌细胞横径增大,心肌纤维增粗、排列紊乱、断裂,核增大,形态不规则,核仁浓染,间质增生等改变苓桂术甘汤组和肾气丸组HE染色改变与模型组相似,且两组病理改变差异不显著。血流动力学参数与假手术组比较,模型组大鼠心率(HR)、左室内压最大上升速率(+dp/dtmax)明显降低(P0.05);左心室舒张压(LVEDP)明显升高(P0.05),提示模型组大鼠舒缩功能不全。与模型组比较,苓桂术甘汤组心率(HR)、左室内压最大上升速率(+dp/dtmax)明显升高,(P0.05);左心室舒张末压(LVEDP)明显降低(P0.05);肾气丸组心率(HR)、左心室收缩压(LVSP)、左室内压最大上升速率(+dp/dtmax)明显升高(P0.05)。提示苓桂术甘汤和肾气丸均能改善模型大鼠血流动力学。苓桂术甘汤组与肾气丸组比较(P0.05)。提示苓桂术甘汤和肾气丸对改善模型大鼠舒缩功能不全这一环节,作用效果差异不显著。结论:苓桂术甘汤和肾气丸均可改善模型大鼠心功能,且两方的干预效果差异不显著。即"同病-同证-异治"是可能存在的。它存在的内涵可能是两方作用于慢性心衰的不同环节。
[Abstract]:This paper is discussed from three aspects: literature review, theoretical research, experimental research. Operation Gan Tang and Shenqi Pill are used in the treatment of heart disease. In clinical application, the effect of Luli Gump soup or kidney qi Pill on chronic heart failure, hypertension and other diseases is studied. In the experimental study, the mechanism of the effect of two parties on the onset of heart disease is mainly discussed from the angle of RAAS system and inflammatory factors. Tang and Shenqi pills have rich clinical practice and a solid foundation of experimental research in the prevention and treatment of heart disease. All of them can improve the "short gas, micro drink", but there are still shortcomings in the study of the connotation of "synopsis of the same disease" in the golden chamber. The interpretation of the original text and the results of the study on "disease and hetero treatment" in recent years have found that the connotation of "common disease and hetero treatment" based on the "common disease and hetero treatment" is not comprehensive, and the "same disease and the same syndrome differentiation" may exist, but the empirical study of "common disease and the same syndrome differentiation" is not perfect. The experiment selected the representative model of "short gas, micro drink" in the experiment. In this paper, the model of heart failure was selected as the representative model of "short gas and micro drink". The empirical study was carried out in two parts: the first part was based on the effect of Luli Gump Decoction and kidney qi pill based on chronic heart failure rat model. Objective: To observe whether the intervention effect of Ling Gui Shu Gan Decoction and Shenqi Pill on chronic heart failure model rats is different. Methods: 30 healthy SD rats were taken and the rat model of chronic heart failure was established by coarctation of abdominal aorta. After 10 sham operations, the model rats were divided into 1 model group, and (2) Luli Gump Decoction group; (3) kidney. Qi pill group, and began to give traditional Chinese medicine gavage for 4 weeks, the model group and sham operation group were gavage with pure water. After.4 weeks, the lung function and arterial blood gas of each group were detected. Results: the results of lung function and blood gas analysis were compared with the sham operation group, the model group was FVC, FEV1/FVC decreased (P0.05), arterial blood pH, Pa0 2, SO2 decreased (P0.05) and PaCO2 increased (P0.05). It suggested that the model rats had cardiac dysfunction. Compared with the model group, the lung function and arterial blood gas of the kidney qi pill group were improved (P0.05). The difference of lung function and blood gas between the Gump Decoction group and the kidney qi pill group was not significant (P0.05). Shenqi Pill can improve the heart function of chronic heart failure rats, that is, it can improve the "short gas". And the difference of the effect of the two parties is not significant. Conclusion: Luli Gump Decoction and kidney qi pill can improve the heart function of the rat model of chronic heart failure, and the difference of the effect of the two parties is not significant, that is, the interpretation of "the same disease and the disease and the treatment" is possible. The second part is based on the slow effect. The purpose of the study is to study the mechanism of Luli Gump Decoction and Shenqi Pill to improve the chronic heart failure from the point of action. Luli Gump soup group; (3) model group: (4) sham operation group. Detection of lung function, arterial blood gas, hemodynamic parameters, myocardial pathology (HE staining) observation, urine volume of rat 24h rats were collected by metabolic cage, Na+, K+, Cl- concentration in urine of rats were detected by automatic analyzer; AQP2 concentration in urine was detected by ELISA method; ELISA method was used to detect PRA and Ang in serum, Ang. II, ALD concentration, concentration of inflammatory factors (IL-6, IL-10, IL-18, IL-1 beta), CRP concentration. Results: compared with the sham group, the results of lung function and blood gas analysis were compared with the sham operation group. The rats in the model group decreased (P0.05), pH, Pa02, Sa02 all decreased. It suggested that the model rats have cardiac dysfunction, that is, "short breath". The model group was compared, the lung function and arterial blood gas of the rats in the kidney qi pill group were improved (P0.05). The results suggested that the two parties could improve the heart function of the rats with chronic heart failure. The lung function and arterial blood gas of the rats in the Gump Decoction group and the kidney qi pill group were compared (P0.05). The difference between the two parties was not significant, and the "short" could improve the "short". The urine volume, urine Na+, K+, Cl- concentration, AQP2 concentration test results compared with the sham operation group, the urine volume decreased (P0.05), the urine Na+, Cl- concentration decreased (P0.05), the K+ concentration increased (P0.05), the urine AQP2 concentration increased (P0.05), suggesting that the model rats had water retention. Compared with the model group, Luli Gump soup was compared with the model group. The urine volume of rats in Shenqi Pill group increased (P0.05), Luli Gump Decoction group, kidney qi pill group Na+, Cl- concentration significantly increased (P0.05), K+ concentration decreased significantly (P0.05), AQP2 concentration in urine of kidney qi pill group decreased (P0.05), suggesting that the above two parties could improve the retention of water in rat model rats and kidney qi pill group and kidney qi pill group rats urine. The difference was not statistically significant (P0.05), suggesting that the difference of water retention in the model rats was not significant. The results of serum PRA, Ang II and ALD concentration in serum were compared with the sham operation group: the arterial blood of rats in the model group was PRA, Ang II, and ALD content increased (P0.05), suggesting the activation of RAAS system in the rat model of heart failure. Compared with the model group: the rats of Luli Gump Decoction group, the rats of kidney qi pill group rats PRA, ALD decreased (P0.05), Ang II decreased not significantly (P0.05), suggesting that the two parties can reduce PRA and ALD generation and inhibit RAAS system activation. Compared with the Luli Gump Decoction group, the kidney qi pill group rats ALD significantly decreased (P0.05). Suggesting that two parties can inhibit ALD raw. It could inhibit the activation of RAAS system, but the effect of kidney qi pill was significant. The results of serum inflammatory factors (IL-6, IL-10, IL-18, IL-1 beta) and CRP concentration were compared with the sham operation group: the serum IL-6, IL-18, IL-10, TNF- a, IL-1 beta and CRP all increased in the model group, suggesting that the inflammatory factors in the model rats were activated. The concentration of IL-6, IL-18, IL-10 and IL-1 beta in the serum of Gump Decoction group decreased (P0.05), and the concentration of IL-6, IL-10 and IL-1 beta in the serum of kidney qi pill group decreased (P0.05). The concentration of IL-10 and IL-18 increased (P0.05) in the kidney qi pill group. To inhibit the inflammatory reaction. Myocardial histopathology was observed in the sham operation group: the size of the myocardium, the shape of the myocardium was normal, the myocardial fibers were arranged regularly. The transverse diameter of the cardiac myocytes in the model group was enlarged, the myocardial fibers were thickened, the rupture, the nucleus increased, the morphology was irregular, the nucleolus concentration, and the interstitial hyperplasia were changed by HE staining in the Gump Decoction group and the kidney qi pill group. Compared with the model group, the pathological changes of the two groups were not significant. Compared with the sham group, the heart rate (HR) and the maximum increase rate of left indoor pressure (+dp/dtmax) decreased significantly (P0.05), and the left ventricular diastolic pressure (LVEDP) was significantly increased (P0.05) in the model group. The heart rate (HR) of Gan Tang Group (P0.05), left ventricular end diastolic pressure (LVEDP) decreased significantly (P0.05), kidney qi pill group heart rate (HR), left ventricular systolic pressure (LVSP), and the maximum rise rate of left ventricular pressure (+dp/ dtmax) increased significantly (P0.05). It suggested that Luli Gump soup and kidney qi pills could improve the blood of model rats. Flow mechanics. Luli Gump Decoction group and kidney qi pill group (P0.05). Suggesting that Ling Gui Shu Gan Decoction and Shenqi Pill have no significant difference in effect of improving the model rats' diastolic dysfunction. Conclusion: Luli Gan Tanghe kidney qi pill can improve the heart function of the model rats, and the difference of the intervention effect of the two parties is not significant. Heteronomy "is possible". The connotation of its existence may be the different links between the two parties acting on chronic heart failure.
【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
本文编号：2128192
[Abstract]:This paper is discussed from three aspects: literature review, theoretical research, experimental research. Operation Gan Tang and Shenqi Pill are used in the treatment of heart disease. In clinical application, the effect of Luli Gump soup or kidney qi Pill on chronic heart failure, hypertension and other diseases is studied. In the experimental study, the mechanism of the effect of two parties on the onset of heart disease is mainly discussed from the angle of RAAS system and inflammatory factors. Tang and Shenqi pills have rich clinical practice and a solid foundation of experimental research in the prevention and treatment of heart disease. All of them can improve the "short gas, micro drink", but there are still shortcomings in the study of the connotation of "synopsis of the same disease" in the golden chamber. The interpretation of the original text and the results of the study on "disease and hetero treatment" in recent years have found that the connotation of "common disease and hetero treatment" based on the "common disease and hetero treatment" is not comprehensive, and the "same disease and the same syndrome differentiation" may exist, but the empirical study of "common disease and the same syndrome differentiation" is not perfect. The experiment selected the representative model of "short gas, micro drink" in the experiment. In this paper, the model of heart failure was selected as the representative model of "short gas and micro drink". The empirical study was carried out in two parts: the first part was based on the effect of Luli Gump Decoction and kidney qi pill based on chronic heart failure rat model. Objective: To observe whether the intervention effect of Ling Gui Shu Gan Decoction and Shenqi Pill on chronic heart failure model rats is different. Methods: 30 healthy SD rats were taken and the rat model of chronic heart failure was established by coarctation of abdominal aorta. After 10 sham operations, the model rats were divided into 1 model group, and (2) Luli Gump Decoction group; (3) kidney. Qi pill group, and began to give traditional Chinese medicine gavage for 4 weeks, the model group and sham operation group were gavage with pure water. After.4 weeks, the lung function and arterial blood gas of each group were detected. Results: the results of lung function and blood gas analysis were compared with the sham operation group, the model group was FVC, FEV1/FVC decreased (P0.05), arterial blood pH, Pa0 2, SO2 decreased (P0.05) and PaCO2 increased (P0.05). It suggested that the model rats had cardiac dysfunction. Compared with the model group, the lung function and arterial blood gas of the kidney qi pill group were improved (P0.05). The difference of lung function and blood gas between the Gump Decoction group and the kidney qi pill group was not significant (P0.05). Shenqi Pill can improve the heart function of chronic heart failure rats, that is, it can improve the "short gas". And the difference of the effect of the two parties is not significant. Conclusion: Luli Gump Decoction and kidney qi pill can improve the heart function of the rat model of chronic heart failure, and the difference of the effect of the two parties is not significant, that is, the interpretation of "the same disease and the disease and the treatment" is possible. The second part is based on the slow effect. The purpose of the study is to study the mechanism of Luli Gump Decoction and Shenqi Pill to improve the chronic heart failure from the point of action. Luli Gump soup group; (3) model group: (4) sham operation group. Detection of lung function, arterial blood gas, hemodynamic parameters, myocardial pathology (HE staining) observation, urine volume of rat 24h rats were collected by metabolic cage, Na+, K+, Cl- concentration in urine of rats were detected by automatic analyzer; AQP2 concentration in urine was detected by ELISA method; ELISA method was used to detect PRA and Ang in serum, Ang. II, ALD concentration, concentration of inflammatory factors (IL-6, IL-10, IL-18, IL-1 beta), CRP concentration. Results: compared with the sham group, the results of lung function and blood gas analysis were compared with the sham operation group. The rats in the model group decreased (P0.05), pH, Pa02, Sa02 all decreased. It suggested that the model rats have cardiac dysfunction, that is, "short breath". The model group was compared, the lung function and arterial blood gas of the rats in the kidney qi pill group were improved (P0.05). The results suggested that the two parties could improve the heart function of the rats with chronic heart failure. The lung function and arterial blood gas of the rats in the Gump Decoction group and the kidney qi pill group were compared (P0.05). The difference between the two parties was not significant, and the "short" could improve the "short". The urine volume, urine Na+, K+, Cl- concentration, AQP2 concentration test results compared with the sham operation group, the urine volume decreased (P0.05), the urine Na+, Cl- concentration decreased (P0.05), the K+ concentration increased (P0.05), the urine AQP2 concentration increased (P0.05), suggesting that the model rats had water retention. Compared with the model group, Luli Gump soup was compared with the model group. The urine volume of rats in Shenqi Pill group increased (P0.05), Luli Gump Decoction group, kidney qi pill group Na+, Cl- concentration significantly increased (P0.05), K+ concentration decreased significantly (P0.05), AQP2 concentration in urine of kidney qi pill group decreased (P0.05), suggesting that the above two parties could improve the retention of water in rat model rats and kidney qi pill group and kidney qi pill group rats urine. The difference was not statistically significant (P0.05), suggesting that the difference of water retention in the model rats was not significant. The results of serum PRA, Ang II and ALD concentration in serum were compared with the sham operation group: the arterial blood of rats in the model group was PRA, Ang II, and ALD content increased (P0.05), suggesting the activation of RAAS system in the rat model of heart failure. Compared with the model group: the rats of Luli Gump Decoction group, the rats of kidney qi pill group rats PRA, ALD decreased (P0.05), Ang II decreased not significantly (P0.05), suggesting that the two parties can reduce PRA and ALD generation and inhibit RAAS system activation. Compared with the Luli Gump Decoction group, the kidney qi pill group rats ALD significantly decreased (P0.05). Suggesting that two parties can inhibit ALD raw. It could inhibit the activation of RAAS system, but the effect of kidney qi pill was significant. The results of serum inflammatory factors (IL-6, IL-10, IL-18, IL-1 beta) and CRP concentration were compared with the sham operation group: the serum IL-6, IL-18, IL-10, TNF- a, IL-1 beta and CRP all increased in the model group, suggesting that the inflammatory factors in the model rats were activated. The concentration of IL-6, IL-18, IL-10 and IL-1 beta in the serum of Gump Decoction group decreased (P0.05), and the concentration of IL-6, IL-10 and IL-1 beta in the serum of kidney qi pill group decreased (P0.05). The concentration of IL-10 and IL-18 increased (P0.05) in the kidney qi pill group. To inhibit the inflammatory reaction. Myocardial histopathology was observed in the sham operation group: the size of the myocardium, the shape of the myocardium was normal, the myocardial fibers were arranged regularly. The transverse diameter of the cardiac myocytes in the model group was enlarged, the myocardial fibers were thickened, the rupture, the nucleus increased, the morphology was irregular, the nucleolus concentration, and the interstitial hyperplasia were changed by HE staining in the Gump Decoction group and the kidney qi pill group. Compared with the model group, the pathological changes of the two groups were not significant. Compared with the sham group, the heart rate (HR) and the maximum increase rate of left indoor pressure (+dp/dtmax) decreased significantly (P0.05), and the left ventricular diastolic pressure (LVEDP) was significantly increased (P0.05) in the model group. The heart rate (HR) of Gan Tang Group (P0.05), left ventricular end diastolic pressure (LVEDP) decreased significantly (P0.05), kidney qi pill group heart rate (HR), left ventricular systolic pressure (LVSP), and the maximum rise rate of left ventricular pressure (+dp/ dtmax) increased significantly (P0.05). It suggested that Luli Gump soup and kidney qi pills could improve the blood of model rats. Flow mechanics. Luli Gump Decoction group and kidney qi pill group (P0.05). Suggesting that Ling Gui Shu Gan Decoction and Shenqi Pill have no significant difference in effect of improving the model rats' diastolic dysfunction. Conclusion: Luli Gan Tanghe kidney qi pill can improve the heart function of the model rats, and the difference of the intervention effect of the two parties is not significant. Heteronomy "is possible". The connotation of its existence may be the different links between the two parties acting on chronic heart failure.
【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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