不同降压药对自发性高血压大鼠血压变异性及动脉粥样硬化的影响

Effect of different antihypertensive drugs on blood pressure variability and atherosclerosis in spontaneously hypertensive rats

  • 摘要: 目的评价氨氯地平、贝那普利和美托洛尔对自发性高血压大鼠(SHR)血压变异性及动脉粥样硬化的影响。方法 40只雄性SHR随机分组为SHR组、SHR+高脂组、氨氯地平组、贝那普利组和美托洛尔组。SHR+高脂组、氨氯地平组、贝那普利组和美托洛尔组通过高脂喂养+维生素D3腹膜注射建立动脉粥样硬化模型。氨氯地平组、贝那普利组和美托洛尔组分别给予苯磺酸氨氯地平10 mg/(kg·d)、盐酸贝那普利10 mg/(kg·d)和酒石酸美托洛尔150 mg/(kg·d)灌胃。在分组前(基线)和干预后第2、4、6、8、10、12周对大鼠进行无创尾部血压监测。完成12周观察期后,取大鼠血清行血脂和高敏C反应蛋白(hsCRP)、髓过氧化物酶(MPO)、脂蛋白相关磷脂酶A2(Lp-PLA2)检测;取胸主动脉制备石蜡病理切片,HE染色,评估动脉粥样硬化程度。结果与美托洛尔组比较,氨氯地平组和贝那普利组总体收缩压标准差(8.07±4.23),(12.20±5.92)比(19.02±4.97)mm Hg,P<0.01和变异系数(5.05±2.67)%,(7.50±3.83)%比(12.00±4.06)%,P<0.01更小,血清Lp-PLA2更低(146.4±18.5),(147.0±24.0)比(169.2±36.8)ng/mL,P<0.05,且胸主动脉粥样硬化病变分级程度更轻。结论氨氯地平和贝那普利较美托洛尔更能减小SHR的血压变异性,减轻动脉粥样硬化的严重程度。

     

    Abstract: Objective To evaluate the effect of amlodipine, benazepril and metoprolol on blood pressure variability and atherosclerosis in high-fat-fed spontaneously hypertensive rats(SHR). Methods Forty male SHRs were randomly divided into SHR group, SHR+hyperlipid group, amlodipine group, benazepril group and metoprolol group. Atherosclerosis models were established in SHR+hyperlipid group, amlodipine group, benazepril group and metoprolol group by high fat feeding and vitamin D3 peritoneal injection. Rats in amlodipine group, benazepril group and metoprolol group were given amlodipine benzenesulfonate 10 mg/(kg·d), benazepril hydrochloride 10 mg/(kg·d) and metoprolol tartrate 150 mg/(kg·d), respectively. Non-invasive tail blood pressure monitoring was performed before grouping(baseline) and 12 weeks after intervention. After 12 observation periods, serum lipids and high sensitivity C reactive protein(hsCRP), myeloperoxidase(MPO), lipoprotein-associated phospholipase 2(Lp-PLA2) were measured and the pathological sections of thoracic aorta were taken to make paraffin sections. HE staining was used to evaluate the degree of atherosclerosis. Results Compared with metoprolol group, the standard deviation(SD) value (8.07±4.23),(12.20±5.92) vs(19.02±4.97) mm Hg and cofficient of variation(CV) (5.05±2.67)%,(7.50±3.83)% vs(12.00±4.06)%, P< 0.01 of systolic blood pressure in amlodipine group and benazepril group were lower, and the serum Lp-PLA2 value (146.4±18.5),(147.0±24.0) vs(169.2±36.8) ng/mL, P<0.05 were lower. The degree of aortic atherosclerosis in thoracic aorta was lower in amlodipine and benazepril group. Conclusion Amlodipine and benazepril can reduce blood pressure variability and reduce the severity of atherosclerosis in SHRs more than metoprolol.

     

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