本文選題：甜菜堿 + 依那普利�。� 參考：《泰山醫(yī)學(xué)院》2014年碩士論文

【摘要】：目的 觀察甜菜堿與依那普利單用及聯(lián)用對腎性高血壓大鼠的降壓作用及對靶器官的保護(hù)作用，初步探討其作用機(jī)制和甜菜堿在高血壓治療中的應(yīng)用前景。 方法 取腎性高血壓大鼠隨機(jī)分為8組，每組10只，分別為模型組，甜菜堿低、中、高劑量組(50、100、200mg/kg)，依那普利組(3mg/kg)，依那普利(3mg/kg)分別與甜菜堿低、中、高劑量(50、100、200mg/kg)聯(lián)用組；另取同批次Wistar大鼠10只作為假手術(shù)對照組。各組大鼠每天灌胃給藥1次，連續(xù)給藥8W，模型組和假手術(shù)組同法給予等容量生理鹽水。 給藥第4和第8周，無創(chuàng)尾套法測定大鼠收縮壓。第8周末次給藥次日，水合氯醛麻醉，取血漿、心臟、主動脈弓、腎臟。心臟留心室部分，即刻稱重，計(jì)算全心室重量指數(shù)(VMI)、左心室重量指數(shù)(LVMI)、右心室重量指數(shù)(RVMI)、左心室壁厚(LVWT)、右心室壁厚(RVWT)、室間隔厚(IVST)。左心室、腎臟橫切為兩部分，心尖部、腎臟上部常規(guī)制作石蠟切片，進(jìn)行HE染色，其余部分用作勻漿。測定血漿同型半胱氨酸(Hcy)的含量；分別測定血漿、心臟、腎臟組織勻漿中活性氧(ROS)、丙二醛(MDA)、一氧化氮(NO)、血管緊張素II (Ang II)、內(nèi)皮素1(ET-1)的含量及超氧化物歧化酶(SOD)、谷胱甘肽過氧化物酶(GSH-Px)、腎素(Renin)的活性。 結(jié)果 1甜菜堿與依那普利單用及聯(lián)用對血壓的影響模型組大鼠在實(shí)驗(yàn)期間始終保持穩(wěn)定的高血壓狀態(tài)。依那普利單用及聯(lián)用不同劑量甜菜堿組大鼠血壓明顯降低(P0.01)，依那普利單用與聯(lián)用組的降壓作用無明顯差異，甜菜堿各劑量單用對血壓無明顯影響(P＞0.05)。表明甜菜堿對腎性高血壓大鼠無降壓作用，對依那普利的降壓作用亦無無明顯影響。 2甜菜堿與依那普利單用及聯(lián)用對靶器官的保護(hù)作用與模型組比較，甜菜堿單用、依那普利單用及兩藥聯(lián)用均可逆轉(zhuǎn)高血壓引起的左心室重構(gòu)，各用藥組的VMI、LVMI和LVWT均明顯降低(P0.01)；與兩種藥物單用組比較，兩藥聯(lián)用對改善左心室重構(gòu)具有明顯協(xié)同作用(P0.05)，其中甜菜堿高劑量與依那普利聯(lián)用組的各項(xiàng)心臟參數(shù)與對照組一致。HE染色結(jié)果表明，甜菜堿單用、依那普利單用及兩藥聯(lián)用組與模型組相比，模型組靶器官的病理狀態(tài)明顯得到改善，具有保護(hù)作用。 3甜菜堿與依那普利單用及聯(lián)用對Hcy的影響實(shí)驗(yàn)結(jié)果表明，甜菜堿單用及與依那普利聯(lián)用可以降低腎性高血壓大鼠血漿Hcy含量(P0.05，P0.01)，依那普利單用無明顯降低作用(P＞0.05)，且兩藥聯(lián)用效果更好(P0.01)。 4甜菜堿與依那普利單用及聯(lián)用抗氧化作用實(shí)驗(yàn)結(jié)果表明，甜菜堿單用、依那普利單用及兩藥聯(lián)用均有抗氧化作用，可降低腎性高血壓大鼠血漿、心肌、腎臟組織中ROS、MDA含量，提高SOD、GSH-Px活力(P0.05，P0.01)；兩藥聯(lián)用具有協(xié)同作用(P0.01)。 5甜菜堿與依那普利單用及聯(lián)用對NO、ET-1含量的影響實(shí)驗(yàn)結(jié)果表明，腎性高血壓模型組大鼠血漿、心肌、腎臟組織ET-1含量明顯升高， NO含量明顯降低，甜菜堿、依那普利單用及與依那普利聯(lián)用組血漿、心肌、腎臟組織中ET-1含量顯著降低，NO含量明顯提高(P0.05，P0.01)，兩藥聯(lián)用具有協(xié)同作用(P0.01)。 6甜菜堿與依那普利單用及聯(lián)用對AngII含量及Renin活性的影響甜菜堿、依那普利單用及與依那普利聯(lián)用可以減少RAS系統(tǒng)的激活，使腎性高血壓大鼠血漿、心肌腎臟組織中AngII含量和腎臟組織中Renin水平降低(P0.05，，P0.01)，兩藥聯(lián)合具有明顯的降低作用(P0.01)。 結(jié)論 1依那普利單用及與甜菜堿聯(lián)用對腎性高血壓大鼠有明顯降壓作用；甜菜堿單用無明顯降壓作用，其對依那普利的降壓作用亦無明顯影響。 2甜菜堿、依那普利單用及兩藥聯(lián)用對腎性高血壓大鼠靶器官具有保護(hù)作用，可以逆轉(zhuǎn)高血壓引起的左心室、主動脈重構(gòu)，減輕腎臟損傷；兩藥聯(lián)用對靶器官的保護(hù)具有協(xié)同作用。 3甜菜堿單用及與依那普利聯(lián)用可以降低腎性高血壓大鼠血漿Hcy含量，依那普利單用無明顯降低作用，表明甜菜堿可以通過降低腎性高血壓大鼠Hcy含量改善靶器官的損傷作用，且兩藥聯(lián)用效果更好。 4甜菜堿、依那普利單用及與依那普利聯(lián)用明顯降低腎性高血壓大鼠血漿、心肌、腎臟組織中ROS、MDA含量，升高SOD、GSH-Px活力，表明甜菜堿對靶器官損傷的保護(hù)作用可能是通過改善體內(nèi)氧化應(yīng)激水平發(fā)揮作用，兩藥聯(lián)用具有協(xié)同作用。 5腎性高血壓模型組大鼠血漿、心肌、腎臟組織ET-1含量明顯升高，NO含量明顯降低，甜菜堿、依那普利單用及與依那普利聯(lián)用組血漿、心肌、腎臟組織中ET-1含量顯著降低，NO含量明顯提高，表明甜菜堿對腎性高血壓大鼠內(nèi)皮功能有改善作用，兩藥聯(lián)用具有協(xié)同作用。 6甜菜堿、依那普利單用及與依那普利聯(lián)用可以降低腎性高血壓大鼠血漿、心肌腎臟組織中AngII含量和腎臟組織中Renin水平，通過調(diào)節(jié)RAS系統(tǒng)來保護(hù)靶器官的損傷。
[Abstract]:objective
To observe the antihypertensive effect of betaine and enalapril on the antihypertensive effect and the protective effect on the target organs of renovascular hypertensive rats, the mechanism of action and the prospect of the application of betaine in the treatment of hypertension were preliminarily discussed.
Method
Rats of renal hypertension were randomly divided into 8 groups, 10 rats in each group, which were model group, low dose of betaine, middle and high dose group (50100200mg/kg), enalapril group (3mg/kg) and enalapril (3mg/kg) combined with betaine low, medium and high dose (50100200mg/kg), and 10 rats of the same batch of Wistar rats were taken as the sham operation control group. Each group rats were given each group. The rats were administrated 1 times a day for 8W, while the model group and the sham operation group were given the same volume of normal saline.
Fourth and eighth weeks, non invasive tail sleeve method was used to determine the systolic pressure of rats. After the eighth week of administration, the next day, chloral hydrate anaesthesia, plasma, heart, aortic arch, kidney, heart left ventricular part, immediate weighing, calculated total ventricular weight index (VMI), left ventricular weight index (LVMI), right ventricular mass index (RVMI), left ventricular wall thickness (LVWT), right ventricular wall Thickness (RVWT), interventricular septum thick (IVST). The left ventricle was divided into two parts, the kidneys were cut into the apical part, the paraffin section was routinely made with paraffin section, HE stained, and the rest used as homogenate. The content of plasma homocysteine (Hcy) was measured; the active oxygen (ROS), malondialdehyde (MDA), nitric oxide (NO), blood vessels in the plasma, heart and kidney tissue homogenate were measured respectively. The contents of tension II (Ang II), endothelin 1 (ET-1), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and renin (Renin) activity.
Result
The effect of 1 betaine and enalapril on the blood pressure in the model group was always stable during the experimental period. The blood pressure of the enalapril alone and the combined use of different doses of betaine group was significantly lower (P0.01). There was no significant difference between the enalapril and the combination group. There was no significant difference in pressure (P > 0.05), indicating that betaine has no antihypertensive effect on renal hypertensive rats, and has no obvious effect on the antihypertensive effect of enalapril.
The protective effect of 2 betaine and enalapril on the target organ was compared with the model group. The single use of betaine, the single use of enalapril and two drugs could reverse the left ventricular remodeling caused by hypertension. The VMI, LVMI and LVWT of each group were significantly decreased (P0.01). Compared with the two medication group, the two drugs combined to improve left ventricle. The reconfiguration had obvious synergism (P0.05), in which the heart parameters of the high dose of betaine and enalapril combined with the control group were in accordance with the control group. The results of.HE staining showed that betaine alone, enalapril single use and two drugs combined with the model group, the target organ of the model group improved obviously and had protective effect.
The effects of 3 betaine and enalapril on the single and combined use of Hcy showed that the combination of betaine and enalapril could reduce the plasma Hcy content (P0.05, P0.01) in rats with renal hypertension (P0.05, P0.01), and the effect of enalapril alone (P > 0.05) was not significantly reduced, and the effect of the two drugs was better (P0.01).
The results of 4 betaine and enalapril alone and combined with antioxidant effects showed that betaine alone, enalapril alone and two drugs all had antioxidant effects, and could reduce the plasma, myocardial and renal tissues of renal hypertensive rats with ROS, MDA content, SOD, GSH-Px (P0.05, P0.01), and two drugs with synergistic effect (P0.01).
The effects of 5 betaine and enalapril on the content of NO and ET-1 showed that the content of ET-1 in the plasma, myocardium and kidney tissue in the renal hypertensive rats was significantly increased, and the content of NO decreased significantly. The content of ET-1 in the plasma, myocardium and kidney tissues of the group of betaine, enalapril and enalapril was significantly reduced, and NO content was reduced. Significantly increased (P0.05, P0.01), synergistic effect of two drugs (P0.01).
The effect of 6 betaine and enalapril on the content of AngII and Renin activity in combination with enalapril, enalapril alone and combined with enalapril can reduce the activation of the RAS system, making the plasma of renal hypertensive rats, the AngII content in the renal tissue and the level of Renin in the kidney tissue decreased (P0.05, P0.01), and the combination of the two drugs is obvious. Reduce the effect (P0.01).
conclusion
1 Bea Knapp Leigh alone and combined with betaine have obvious hypotensive effect on renovascular hypertensive rats; Betaine alone has no obvious antihypertensive effect and has no significant effect on the antihypertensive effect of Bea Knapp Leigh.
2 betaine, enalapril alone and two drugs have protective effects on the target organs of renovascular hypertensive rats, which can reverse the left ventricle, aortic remodeling and reduce renal injury caused by hypertension; the two drugs have synergistic effects on the protection of the target organs.
The combined use of 3 betaine and enalapril can reduce the plasma Hcy content in renovascular hypertensive rats. The effect of enalapril alone is not significantly reduced. It shows that betaine can improve the target organ damage by reducing the Hcy content of renovascular hypertensive rats, and the effect of the two drugs is better.
4 betaine, enalapril alone and combined with enalapril reduced the plasma, myocardial and renal tissue ROS, MDA content and increased the activity of SOD and GSH-Px in renal hypertensive rats, indicating that the protective effect of betaine on target organ damage may be played by improving the level of oxidative stress in the body. The combined use of two drugs has synergistic effect.
The content of ET-1 in plasma, myocardium and kidney tissue of rats with renal hypertension was significantly increased, and the content of NO decreased significantly. The content of ET-1 in plasma, myocardium and renal tissue in the group of betaine and enalapril combined with enalapril and enalapril was significantly reduced, and the content of NO increased significantly, indicating that betaine has improved the endothelial function of renovascular rats, two The combination of drugs has synergistic effect.
6 betaine, enalapril alone and combined with enalapril can reduce the plasma levels of renal hypertensive rats, the content of AngII in the renal tissue and the level of Renin in the renal tissue, and protect the target organ damage by regulating the RAS system.
【學(xué)位授予單位】：泰山醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R965

【共引文獻(xiàn)】

相關(guān)期刊論文 前3條

1 梁遠(yuǎn)紅;林曙光;周燕;王晉明;王芳;余細(xì)勇;;β_1腎上腺受體反義基因?qū)Ω哐獕捍笫笄澳I素、血管緊張素Ⅱ的影響[J];中華高血壓雜志;2007年06期

2 周燕;梁遠(yuǎn)紅;王晉明;魏捷;王芳;謝剛;;運(yùn)動訓(xùn)練聯(lián)合基因治療對自發(fā)性高血壓大鼠心功能的影響[J];中國康復(fù)醫(yī)學(xué)雜志;2007年05期

3 李先偉;楊解人;朱蕭俊;;芝麻素對腎性高血壓大鼠血流動力學(xué)、心肌一氧化氮和內(nèi)皮素-1的影響[J];中國實(shí)驗(yàn)方劑學(xué)雜志;2007年04期

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