氯沙坦对自发性高血压大鼠前列腺增生作用的实验研究  

Inhibitory effect of losartan on prostatic hyperplasia in spontaneous hypertension rats and its pathophysiological mechanism

作　　者：沈芳[1] 董莉妮[1] 张湘瑜[1] 赵晓昆[1] 曾小芳[1] 屈晓冰[1] 

机构地区：[1]中南大学湘雅二医院老年医学科,湖南长沙410011

出　　处：《中华男科学杂志》2012年第7期600-605,共6页National Journal of Andrology

基　　金：中央保健委项目(B2009A058);湖南省科技厅项目(2009FJ3076);长沙市重点项目(K0902169-31)~~

摘　　要：目的:研究氯沙坦对自发性高血压大鼠(SHR)前列腺增生的作用及机制。方法:采用36只雄性SHR,随机分为氯沙坦高剂量干预组[30 mg/(kg.d)]、氯沙坦低剂量干预组[15 mg/(kg.d)]及对照组,每组12只。测量大鼠体重及尾动脉基础血压。分别予以氯沙坦混悬液及蒸馏水灌胃。干预6周后,测量各组SHR体重及尾动脉血压,麻醉动物,心脏取血待测,分离大鼠前列腺并称重后行组织固定、包埋、切片。电镜观察前列腺细胞超微结构。酶联免疫吸附法测定大鼠血清血管紧张素Ⅱ(AngⅡ)、胰岛素样生长因子-1(IGF-1)、白介素-6(IL-6)水平;免疫组织化学法测定大鼠前列腺组织中内皮源性一氧化氮合酶(eNOS)表达阳性率。结果:与对照组比较,氯沙坦干预后低剂量和高剂量干预组SHR尾动脉收缩压明显降低[(203.75±10.28)mmHg vs(184.54±16.90)mmHg,P=0.013和(203.75±10.28)mmHg vs(166.88±14.74)mmHg,P<0.001],舒张压亦明显降低[(151.58±9.96)mmHg vs(136.71±14.28)mmHg,P=0.022和(151.58±9.96)mmHg vs(122.71±11.56)mmHg,P<0.001]。SHR前列腺重量在低和高剂量干预组中均比对照组明显降低[(0.64±0.10)vs(0.73±0.08)mg,P=0.011和(0.50±0.17)vs(0.73±0.08)mg,P<0.001];电镜观察示氯沙坦低剂量干预后基底细胞及柱状上皮细胞水肿,间质中纤维母细胞核异染色质浓集趋边、核周隙增宽,线粒体、内质网减少;氯沙坦高剂量干预组超微结构紊乱程度较低剂量干预组更明显;氯沙坦低剂量干预组、高剂量干预组血清AngⅡ水平较对照组均明显升高[(61.32±2.49)vs(54.85±7.20)pg/ml,P=0.021和(65.49±6.78)vs(54.85±7.20)pg/ml,P<0.001)];氯沙坦高剂量干预组血清IGF-1水平较对照组下降[(1.50±0.11)vs(1.60±0.10)ng/ml,P=0.03)];氯沙坦干预后血清IL-6水平较对照组无明显变化;免疫组化显示氯沙坦干预后大鼠前列腺组织eNOS表达阳性率较对照组明显增高,高剂量干预组较低剂量干预组升高更显著,氯沙坦干预组与�Objective： To investigate the effect of losartan on prostatic hyperplasia in spontaneous hypertension rats （SHRs） and its pathophysiological mechanism. Methods： We randomly divided 36 male SHRs into three groups of equal number to be treated intragastricaUy with high-dose losartan （30 mg per kg per d）, low-dose losartan （15 mg per kg per d） and distilled water （control group）. After 6 weeks of intervention, we measured the body weight and tail artery blood pressure of the rats and compared them with the baseline data. We collected blood from the heart for determination of the levels of serum angiotensin lI （ Ang II ）, insulin-like growth factor-1 （IGF-1） and interleukin-6 （IL-6） by enzyme-linked immunosorbent assay （ELISA）, and harvested their prostates for measurement of their weight, observation of the tissue ultrastructures under the electron microscope and detection of the expression of endothelial nitric oxide synthase （eNOS） in the prostate tissue by immunohistochemistry. Results： Compared with the control group, the low- and high-dose losartan groups showed significant decreases in systolic blood pressure （ [ 203.75 ±10.28 ] vs [ 184.54 ± 16.90] mmHg, P=0. 013; [203.75 ±10.28] vs [166.88 ±14.74] mmHg, P=0. 001） and diastolic blood pressure （[151.58 ± 9.96] vs [136.71 ±14.28] mmHg, P=0.022; [151.58 ±9.96] vs [122.71±11.56] mmHg, P〈0. 001） of the lower tail artery after treatment, as well as in the prostate weight （ [ 0. 73± 0.08 ] vs [ 0. 64±0. 10 ] mg, P = 0. 011 ; [ 0. 73 ± 0.08 ] vs [ 0.50 ± 0. 17 ] mg, P 〈 0. 001 ）. Electron microscopy revealed edema of the basal and columnar epithelial ceils, concentrated and marginated heterochromatin and widened nuclear gap of interstitial fibroblast nuclei, and reduced mitochondria and endoplasmic reticula in the lowdose losartan group, and even more obvious in the high-dose group. The level of serum Ang II was remarkably higher in the low- and high-dose losartan groups than in the control （ [ 6

关 键 词：良性前列腺增生 氯沙坦 胰岛素样生长因子-1 血管紧张素Ⅱ 

分 类 号：R965[医药卫生—药理学]