不同遗传性高血压大鼠的主动脉超微结构与血管功能损伤  

The ultrastructure changes and vascular dysfunction in aorta from different hereditary hypertensive rats

作　　者：陈浥尘 蒋柳萍[2] 车在前[3] 沈伟利[4] 陈红[1] 臧敏华[1] 陆琴[1] 郑林[1] 叶朝阳[5] 東野英明 山西恭辅 穆罕默德吉福 山西博道 岡村春树 

机构地区：[1]上海交通大学医学院药理学教研室,中国上海200025 [2]解放军第八五医院外科,中国上海200025 [3]上海交通大学附属瑞金医院急诊科,中国上海200025 [4]上海市高血压研究所及上海市血管生物学重点实验室,中国上海200025 [5]长征医院肾内科,中国上海200025 [6]東淀川病院,日本大阪 [7]Harima Sanatorium病院,日本兵库675-1121

出　　处：《中华高血压杂志》2014年第8期728-736,共9页Chinese Journal of Hypertension

基　　金：国家自然科学基金资助项目(31171099、30971154及30770848)

摘　　要：背景与目的高血压及高胰岛素血症是导致心血管病变的主要因素。然而高血压大血管病变的超微结构、代谢异常与同期血管功能变化的对比研究缺乏。该实验研究正常及两种遗传性高血压大鼠主动脉超微结构和相应血管功能病变、血糖及胰岛素变化。方法实验选用雄性京都种Wistar大鼠（WKY）、自发性高血压大鼠（SHR）及脑卒中易发型自发性高血压大鼠（SHRSP）。饲养至6-8月龄,每组动物8-10只。测定血压、血胰岛素与血糖水平,分别采用离体血管张力方法测定血管功能,采用光镜及透射电镜方法观察血管内膜、中膜及外膜各层结构变化,测定内膜及内膜中层厚度。结果 SHR及SHRSP收缩压、血清胰岛素水平较WKY升高,SHRSP升高较SHR明显[收缩压：SHR（193±12）、SHRSP（276±20）比WKY（123±9）mm Hg;血清胰岛素：SHR（3.06±0.66）、SHRSP（4.69±0.54）比WKY（2.11±0.27）μg/L,均P〈0.01]。SHR、SHRSP血管内膜及中膜显著增厚[SHR（4.23±0.31）、SHRSP（5.89±0.40）比WKY（2.24±0.12）μm,均P〈0.01],伴有血管内皮依赖及非内皮依赖性舒张功能下降,以SHRSP下降最明显,SHRSP主动脉对α受体激动剂诱导的收缩反应减弱而对高钾的收缩反应增强,SHR对α受体激动剂及高钾诱导的收缩反应均增强。SHR/SHRSP增厚的内膜为内膜下层,由无定形基质、胶原纤维及弹力纤维构成,SHRSP内膜可见水肿及内皮细胞坏死,伴大量单核-巨噬细胞浸润。SHRSP饲养至6-8月脑卒中死亡发生率73.3%,部分SHRSP存活者镜下可见血管局部动脉瘤形成与弹力纤维板断裂,主动脉壁各层胶原纤维呈弥漫变性斑点状钙化（37.5%）。同龄SHR均无死亡、血管未见动脉瘤或胶原钙化。结论严重高血压可导致大血管管壁各层增厚,组织炎症、坏死、胶原钙化与相应的收缩和舒张功能损害;高血压时伴随的高胰岛素血症可能促进血管增殖性病变。Background and objective Hypertension and hyperinsulinemia are the major factors for large vessel lesions and poor cardiovascular outcome. However, there were few comparison studies on vascular ultrastructure, vessel function and metabolic state in normal and hypertensive rats. This study examined the ultrastructure of aortic wall, vessel function , blood glucose, and serum insulin level in normal and hereditary hypertensive rats. Methods Male Wistar Kyoto rats （ WKY ）, spontaneously hypertensive rats （ SHR）, and stroke-prone SHR （SHRsp） at 6 to 8 months were used for experiments （n= 8-10 each group）. Thoracic aortas were dissected for function tests or fixed in 2 % glutaraldehyde for transmission electron microscope study. Three layers of aorta and the intima thickness were closely examined. Intima-media thickness was measured with micrographs taken （5 points per graph and 8--10 random graphs per specimen）. Results The blood pressure of hypertensive rats, especially SHRsp, increased markedly [systolic blood pressure. WKY （ 123 ± 9 ） mm Hg, SHR （ 193 ± 12 ） mm Hg, SHRsp （276±20）mm Hg, P〈0.01]. Hypertensive rats also had significantly elevated serum insulin levels [insulin： WKY （2.11±0.27）μg/L, SHR （3.06±0.66）μg/L, SHRsp（4.69±0.54）μg/L, P〈0.01]. Endothelium-de- pendent and endothelium-independent vasodilatations were reduced significantly in both SHR and SHRsp. The aorta of SHR showed increased contraction reaction to both high potassium and a-receptor agonist. The aorta of SHRsp showed potassium-induced contraction increased, but the a-receptor agonist-induced contraction decreased. In both SHR and SHRsp there were significant sub-endothelial hyperplasia and intima-media thickening [intima thickness values： WKY （2.24±0.12）μm, SHR （4.23±0.31）μm （P〈0.01 vs WKY）, SHRsp （5.89±0.40）μm （P〈0.01 vs WKY and SHR）-1. Seventy three point three percent of SHRsp died of stroke. SHRsp had the most significant intima inflammation and necr

关 键 词：高血压 主动脉超微结构 胶原 钙化 高胰岛素血症 

分 类 号：R544.1[医药卫生—心血管疾病]