【摘要】：本論文從三個(gè)方面進(jìn)行論述:文獻(xiàn)綜述、理論研究、實(shí)驗(yàn)研究。文獻(xiàn)綜述方面:苓桂術(shù)甘湯和腎氣丸均見于《金匱要略》:"夫短氣,有微飲,當(dāng)從小便去之,苓桂術(shù)甘湯主之,腎氣丸亦主之。"類似原文被視為《金匱》"同病異治"的典范。后世常將苓桂術(shù)甘湯和腎氣丸用于治療心系疾病。在臨床應(yīng)用方面多是分別研究苓桂術(shù)甘湯或腎氣丸對慢性心力衰竭、高血壓等疾病的治療作用;在實(shí)驗(yàn)研究方面,多是從RAAS系統(tǒng)、炎癥因子等角度分別探討兩方對心系疾病起效的作用機(jī)制。苓桂術(shù)甘湯和腎氣丸在防治心系疾病方面有較豐富的臨床實(shí)踐及較扎實(shí)的實(shí)驗(yàn)研究基礎(chǔ),均能改善"短氣,微飲",然《金匱》"同病異治"內(nèi)涵的研究尚有不足。理論研究方面:①通過分析《黃帝內(nèi)經(jīng)》、《金匱要略》中有關(guān)"同病異治"的論述和歷代醫(yī)家對原文的解讀,及近年來有關(guān)"同病異治"的研究成果發(fā)現(xiàn),基于"同病異證異治"的"同病異治"內(nèi)涵是不全面的,"同病同證異治"是可能存在的,但對"同病同證異治"的實(shí)證研究尚不完善。②現(xiàn)代醫(yī)家從飲邪角度論治心衰取得了很好的療效,故本實(shí)驗(yàn)選取心衰為"短氣,微飲"的代表模型。實(shí)驗(yàn)研究方面:本論文選取心衰模型為"短氣,微飲"代表性模型,開展"同病異治"內(nèi)涵的實(shí)證研究。主要分兩部分進(jìn)行:第一部分基于慢性心衰大鼠模型的苓桂術(shù)甘湯和腎氣丸"同病異治"之作用比較研究目的:觀察苓桂術(shù)甘湯和腎氣丸對慢性心衰模型大鼠的干預(yù)作用是否有差異。方法:取30只健康SD大鼠,利用腹主動脈縮窄法建立慢性心衰大鼠模型,另取10只行假手術(shù)。2周后將模型大鼠隨機(jī)分為①模型組;②苓桂術(shù)甘湯組;③腎氣丸組,并開始給予中藥灌胃,持續(xù)4周,模型組與假手術(shù)組以純凈水灌胃,各給藥組灌胃相應(yīng)中藥。4周后,檢測各組大鼠的肺功能、動脈血?dú)�。結(jié)果:肺功能與血?dú)夥治鰴z測結(jié)果與假手術(shù)組比較,模型組大鼠FVC、FEV1/FVC均降低(P0.05),動脈血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礙。與模型組比較,苓桂術(shù)甘湯組、腎氣丸組大鼠肺功能和動脈血?dú)饩懈纳?P0.05)。苓桂術(shù)甘湯組和腎氣丸組大鼠肺功能和動脈血?dú)獗容^,差異不顯著(P0.05)。提示苓桂術(shù)甘湯與腎氣丸均可改善慢性心衰大鼠的心功能,即能改善"短氣"。且兩方作用效果差異不顯著。結(jié)論:苓桂術(shù)甘湯和腎氣丸均可改善慢性心衰模型大鼠的心功能,且兩方效果差異不顯著,即"同病-同病-異治"的解讀是可能存在的。第二部分基于慢性心衰大鼠模型的苓桂術(shù)甘湯和腎氣丸"同病異治"之內(nèi)涵研究目的:從作用環(huán)節(jié)角度探討苓桂術(shù)甘湯和腎氣丸改善慢性心衰的機(jī)制,為"同病異治"內(nèi)涵研究提供實(shí)證依據(jù)。方法:模型建立、給藥(同第一部分);實(shí)驗(yàn)隨機(jī)分為①腎氣丸組;②苓桂術(shù)甘湯組;③模型組:④假手術(shù)組。檢測肺功能、動脈血?dú)�、血流動力學(xué)參數(shù);心肌病理(HE染色)觀察;用代謝籠收集大鼠24h大鼠尿量;用全自動分析儀檢測各組大鼠尿液中Na+、K+、Cl-濃度;ELISA法檢測尿液中AQP2濃度;ELISA法檢測血清中PRA、AngⅡ、ALD 濃度、炎癥因子(IL-6、IL-10、IL-18、IL-1β)濃度、CRP 濃度。結(jié)果:肺功能與血?dú)夥治鰴z測結(jié)果與假手術(shù)組比較,模型組大鼠FVC、FEV1/FVC均降低(P0.05),動脈血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礙,即存在"短氣"。與模型組比較,苓桂術(shù)甘湯組、腎氣丸組大鼠肺功能和動脈血?dú)饩懈纳?P0.05)。提示上述兩方均可改善慢性心衰大鼠的心功能。苓桂術(shù)甘湯組和腎氣丸組大鼠肺功能和動脈血?dú)獗容^(P0.05)。提示兩方作用效果差異不顯著,兩方均能改善"短氣",即可"同病異治"。尿量、尿液中Na+、K+、Cl-濃度、AQP2濃度檢測結(jié)果與假手術(shù)組比較,模型組大鼠尿量減少(P0.05),尿Na+、Cl-濃度降低(P0.05),K+濃度明顯升高(P0.05),尿中AQP2濃度升高(P0.05),提示模型大鼠存在水液潴留。與模型組比較,苓桂術(shù)甘湯組、腎氣丸組大鼠尿量增多(P0.05),苓桂術(shù)甘湯組、腎氣丸組大鼠Na+、Cl-濃度明顯升高(P0.05),K+濃度明顯降低(P0.05),腎氣丸組大鼠尿中AQP2濃度降低(P0.05),提示上述兩方均有改善模型大鼠水液潴留的作用。苓桂術(shù)甘湯組與腎氣丸組大鼠尿中離子比較,差異不具有統(tǒng)計(jì)學(xué)意義(P0.05),提示苓桂術(shù)甘湯和腎氣丸對模型大鼠水液潴留作用差異不顯著。血清中PRA、AngⅡ、ALD濃度檢測結(jié)果與假手術(shù)組比較:模型組大鼠動脈血PRA、AngⅡ、ALD含量均升高(P0.05),提示心衰模型大鼠RAAS系統(tǒng)激活。與模型組比較:苓桂術(shù)甘湯組大鼠、腎氣丸組大鼠組大鼠PRA、ALD均降低(P0.05),AngⅡ降低不明顯(P0.05),提示上述兩方均有降低PRA和ALD生成,抑制RAAS系統(tǒng)激活作用。與苓桂術(shù)甘湯組比較,腎氣丸組大鼠ALD明顯降低(P0.05)。提示兩方均能抑制ALD生成從而抑制RAAS系統(tǒng)激活這一環(huán)節(jié),但腎氣丸作用顯著。血清中炎癥因子(IL-6、IL-10、IL-18、IL-1β)、CRP濃度檢測結(jié)果與假手術(shù)組比較:模型組大鼠血清中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癥因子激活。與模型組比較:苓桂術(shù)甘湯組大鼠血清中IL-6、IL-18、IL-10、IL-1β濃度均降低(P0.05),腎氣丸組大鼠血清中IL-6、IL-10、IL-1β濃度降低(P0.05)。與苓桂術(shù)甘湯組比較,腎氣丸組大鼠IL-10、IL-18濃度升高(P0.05)。提示苓桂術(shù)甘湯明顯作用于降低血清中IL-10、IL-18濃度這一環(huán)節(jié),從而抑制炎癥反應(yīng)。心肌組織病理觀察假手術(shù)組:心肌細(xì)胞大小、形態(tài)正常,心肌纖維排列整齊。模型組心肌細(xì)胞橫徑增大,心肌纖維增粗、排列紊亂、斷裂,核增大,形態(tài)不規(guī)則,核仁濃染,間質(zhì)增生等改變苓桂術(shù)甘湯組和腎氣丸組HE染色改變與模型組相似,且兩組病理改變差異不顯著。血流動力學(xué)參數(shù)與假手術(shù)組比較,模型組大鼠心率(HR)、左室內(nèi)壓最大上升速率(+dp/dtmax)明顯降低(P0.05);左心室舒張壓(LVEDP)明顯升高(P0.05),提示模型組大鼠舒縮功能不全。與模型組比較,苓桂術(shù)甘湯組心率(HR)、左室內(nèi)壓最大上升速率(+dp/dtmax)明顯升高,(P0.05);左心室舒張末壓(LVEDP)明顯降低(P0.05);腎氣丸組心率(HR)、左心室收縮壓(LVSP)、左室內(nèi)壓最大上升速率(+dp/dtmax)明顯升高(P0.05)。提示苓桂術(shù)甘湯和腎氣丸均能改善模型大鼠血流動力學(xué)。苓桂術(shù)甘湯組與腎氣丸組比較(P0.05)。提示苓桂術(shù)甘湯和腎氣丸對改善模型大鼠舒縮功能不全這一環(huán)節(jié),作用效果差異不顯著。結(jié)論:苓桂術(shù)甘湯和腎氣丸均可改善模型大鼠心功能,且兩方的干預(yù)效果差異不顯著。即"同病-同證-異治"是可能存在的。它存在的內(nèi)涵可能是兩方作用于慢性心衰的不同環(huán)節(jié)。
[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.
【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R222.3

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