高血压前期氯沙坦干预对成年自发性高血压大鼠阻力血管重塑及血管紧张素Ⅱ1型受体表达的影响  

The effect of prehypertensive losartan treatment on resistance vessel remodeling and angiotensin Ⅱ type 1 receptor expression in adult spontaneously hypertensive rats

作　　者：王庭俊[1] 陈婉茹 林旭 练桂丽 许昌声 王华军 谢良地[1,2,3] WANG Ting-jun;CHEN Wan-ru;LIN Xu;LIAN Gui-li;XU Chang-sheng;WANG Hua-jun;XIE Liang-di(Geriatric Department,The First Affiliated Hospital of Fujian Medical University,Fuzhou Fujian 350005,China;不详)

机构地区：[1]福建医科大学附属第一医院老年科,福建福州350005 [2]福建省高血压研究所,福建福州350005 [3]福建医科大学附属第一医院全科医学科,福建福州350005

出　　处：《中华高血压杂志》2019年第11期1047-1053,共7页Chinese Journal of Hypertension

基　　金：国家自然科学基金（81870316）;福建省中青年骨干人才培养项目（2017-ZQN-44）

摘　　要：目的观察高血压前期氯沙坦干预对成年自发性高血压大鼠(SHR)阻力血管重塑和血管紧张素Ⅱ(AngⅡ)1型受体(AT1R)表达的影响,探讨AT1R表达、阻力血管重塑与早期干预引起的大鼠血压变化之间的内在关系。方法4周龄的Wistar-kyoto(WKY)大鼠和SHR各16只,分别随机分为2组,共4组:WKY组、WKY氯沙坦干预组、SHR组、SHR氯沙坦干预组。干预组大鼠从4周龄开始给予氯沙坦30 mg/(kg·d)灌胃至10周龄,然后停药,尾套法监测收缩压。26周龄的大鼠分离肠系膜三级动脉,HE染色后观察血管结构,PowerLab生物信息采集系统记录血管舒张功能,实时荧光定量聚合酶链反应(PCR)及Western-blot检测血管中AT1R mRNA和蛋白表达,酶联免疫吸附试验(ELISA)法检测血浆和肠系膜动脉中AngⅡ水平。结果10周龄以后,SHR氯沙坦干预组的收缩压明显低于SHR组[26周:(208±12)比(226±11)mm Hg,P=0.018]。26周龄时,与SHR组相比,SHR氯沙坦干预组的肠系膜三级动脉的管壁厚度/管腔半径(0.17±0.03比0.29±0.08,P<0.001)和管壁面积/管腔面积(0.33±0.08比0.47±0.10,P=0.001)较小,内皮依赖性血管舒张功能的最大舒张反应较强[(69.13±4.67)%比(43.87±3.31)%,P<0.001],敏感性指标pD2较高(5.28±0.17比4.76±0.19,P=0.007),非内皮依赖性血管舒张反应的pD2也高(6.71±0.17比5.47±0.16,P<0.001)。SHR氯沙坦干预组肠系膜动脉中AT1R的a亚型mRNA(3.50±0.90比5.01±1.02,P<0.001)及AT1R蛋白表达(0.35±0.10比0.50±0.15,P=0.003)低于SHR组,而血浆和肠系膜动脉中AngⅡ水平高于SHR组(P<0.05)。10周龄时,WKY氯沙坦干预组收缩压低于WKY组[(104±6)比(122±7)mm Hg,P=0.025]。但14周龄以后,WKY氯沙坦干预组与WKY组间的收缩压及上述血管指标的差异无统计学意义(P>0.05)。结论高血压前期氯沙坦干预延缓成年SHR血压升高与阻力血管重塑改善、AT1R表达下调有关。Objective To explore the effect of prehypertensive losartan treatment on resistance vessel remodeling and angiotensinⅡ(AngⅡ)type 1 receptor(AT1R)expression in adult spontaneously hypertensive rats(SHR),and to investigate the relationship between the change of blood pressure induced by the early treatment and AT1R expression,resistance vessel remodeling.Methods Four-week-old Wistar-kyoto(WKY)rats and SHR were randomly divided into 2 groups respectively,and a total of 4 groups with 8 rats in each group were as following:WKY,losartan-treated WKY,SHR and losartan-treated SHR,losartan was administrated to animal by gavage from 4 weeks old to 10 weeks old in losartan-treated rats.After withdrawal,blood pressure was monitored by the tail-cuff method.The rats were followed up till 26 weeks old,and they were sacrificed to determine parameters.The third grade mesenteric arteries were isolated and the following measurements were carried out:the structure of vessel was observed by HE staining,relaxation reactivity of vessel was measured by PowerLab biology signal analytical system as endothelium-dependent relaxation and endothelium-independent relaxation.AT1R mRNA was determined by real-time polymerase chain reaction(PCR),and AT1R protein expression was evaluated by Western-blot.Enzyme linked immunosorbent assay(ELISA)kit was used to assay AngⅡlevels in plasma and mesenteric arteries.Results Since 10 weeks old,systolic blood pressure in losartan-treated SHR had been lower than that in SHR[26 weeks old:(208±12)vs(226±11)mm Hg,P=0.018].At the age of 26 weeks old,wall thickness to lumen radius(0.17±0.03 vs 0.29±0.08,P<0.001)and wall area to lumen area of vessel(0.33±0.08 vs 0.47±0.10,P=0.001)in losartan-treated SHR were significantly lower than those in SHR.Maximum relaxation reactivity of endothelium-dependent relaxation[(69.13±4.67)%vs(43.87±3.31)%,P<0.001]and its pD2,a sensitive index(5.28±0.17 vs 4.76±0.19,P=0.007)increased in losartan-treated SHR compared with those in SHR.PD2 of endothelium-independent rel

关 键 词：高血压前期 氯沙坦 阻力血管 血管重塑 血管紧张素Ⅱ1型受体 

分 类 号：R544.1[医药卫生—心血管疾病]