甜菜碱与依那普利单用及联用对肾性高血压大鼠的治疗作用及其机制

发布时间：2018-06-13 05:34

本文选题：甜菜碱 + 依那普利　；参考：《泰山医学院》2014年硕士论文

【摘要】：目的观察甜菜碱与依那普利单用及联用对肾性高血压大鼠的降压作用及对靶器官的保护作用，初步探讨其作用机制和甜菜碱在高血压治疗中的应用前景。方法取肾性高血压大鼠随机分为8组，每组10只，分别为模型组，甜菜碱低、中、高剂量组(50、100、200mg/kg)，依那普利组(3mg/kg)，依那普利(3mg/kg)分别与甜菜碱低、中、高剂量(50、100、200mg/kg)联用组；另取同批次Wistar大鼠10只作为假手术对照组。各组大鼠每天灌胃给药1次，连续给药8W，模型组和假手术组同法给予等容量生理盐水。给药第4和第8周，无创尾套法测定大鼠收缩压。第8周末次给药次日，水合氯醛麻醉，取血浆、心脏、主动脉弓、肾脏。心脏留心室部分，即刻称重，计算全心室重量指数(VMI)、左心室重量指数(LVMI)、右心室重量指数(RVMI)、左心室壁厚(LVWT)、右心室壁厚(RVWT)、室间隔厚(IVST)。左心室、肾脏横切为两部分，心尖部、肾脏上部常规制作石蜡切片，进行HE染色，其余部分用作匀浆。测定血浆同型半胱氨酸(Hcy)的含量；分别测定血浆、心脏、肾脏组织匀浆中活性氧(ROS)、丙二醛(MDA)、一氧化氮(NO)、血管紧张素II (Ang II)、内皮素1(ET-1)的含量及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、肾素(Renin)的活性。结果 1甜菜碱与依那普利单用及联用对血压的影响模型组大鼠在实验期间始终保持稳定的高血压状态。依那普利单用及联用不同剂量甜菜碱组大鼠血压明显降低(P0.01)，依那普利单用与联用组的降压作用无明显差异，甜菜碱各剂量单用对血压无明显影响(P＞0.05)。表明甜菜碱对肾性高血压大鼠无降压作用，对依那普利的降压作用亦无无明显影响。 2甜菜碱与依那普利单用及联用对靶器官的保护作用与模型组比较，甜菜碱单用、依那普利单用及两药联用均可逆转高血压引起的左心室重构，各用药组的VMI、LVMI和LVWT均明显降低(P0.01)；与两种药物单用组比较，两药联用对改善左心室重构具有明显协同作用(P0.05)，其中甜菜碱高剂量与依那普利联用组的各项心脏参数与对照组一致。HE染色结果表明，甜菜碱单用、依那普利单用及两药联用组与模型组相比，模型组靶器官的病理状态明显得到改善，具有保护作用。 3甜菜碱与依那普利单用及联用对Hcy的影响实验结果表明，甜菜碱单用及与依那普利联用可以降低肾性高血压大鼠血浆Hcy含量(P0.05，P0.01)，依那普利单用无明显降低作用(P＞0.05)，且两药联用效果更好(P0.01)。 4甜菜碱与依那普利单用及联用抗氧化作用实验结果表明，甜菜碱单用、依那普利单用及两药联用均有抗氧化作用，可降低肾性高血压大鼠血浆、心肌、肾脏组织中ROS、MDA含量，提高SOD、GSH-Px活力(P0.05，P0.01)；两药联用具有协同作用(P0.01)。 5甜菜碱与依那普利单用及联用对NO、ET-1含量的影响实验结果表明，肾性高血压模型组大鼠血浆、心肌、肾脏组织ET-1含量明显升高， NO含量明显降低，甜菜碱、依那普利单用及与依那普利联用组血浆、心肌、肾脏组织中ET-1含量显著降低，NO含量明显提高(P0.05，P0.01)，两药联用具有协同作用(P0.01)。 6甜菜碱与依那普利单用及联用对AngII含量及Renin活性的影响甜菜碱、依那普利单用及与依那普利联用可以减少RAS系统的激活，使肾性高血压大鼠血浆、心肌肾脏组织中AngII含量和肾脏组织中Renin水平降低(P0.05，，P0.01)，两药联合具有明显的降低作用(P0.01)。结论 1依那普利单用及与甜菜碱联用对肾性高血压大鼠有明显降压作用；甜菜碱单用无明显降压作用，其对依那普利的降压作用亦无明显影响。 2甜菜碱、依那普利单用及两药联用对肾性高血压大鼠靶器官具有保护作用，可以逆转高血压引起的左心室、主动脉重构，减轻肾脏损伤；两药联用对靶器官的保护具有协同作用。 3甜菜碱单用及与依那普利联用可以降低肾性高血压大鼠血浆Hcy含量，依那普利单用无明显降低作用，表明甜菜碱可以通过降低肾性高血压大鼠Hcy含量改善靶器官的损伤作用，且两药联用效果更好。 4甜菜碱、依那普利单用及与依那普利联用明显降低肾性高血压大鼠血浆、心肌、肾脏组织中ROS、MDA含量，升高SOD、GSH-Px活力，表明甜菜碱对靶器官损伤的保护作用可能是通过改善体内氧化应激水平发挥作用，两药联用具有协同作用。 5肾性高血压模型组大鼠血浆、心肌、肾脏组织ET-1含量明显升高，NO含量明显降低，甜菜碱、依那普利单用及与依那普利联用组血浆、心肌、肾脏组织中ET-1含量显著降低，NO含量明显提高，表明甜菜碱对肾性高血压大鼠内皮功能有改善作用，两药联用具有协同作用。 6甜菜碱、依那普利单用及与依那普利联用可以降低肾性高血压大鼠血浆、心肌肾脏组织中AngII含量和肾脏组织中Renin水平，通过调节RAS系统来保护靶器官的损伤。
[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.
【学位授予单位】：泰山医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R965

【共引文献】