【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。更多还原

【Abstract】 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 6to 8months 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(5points 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-dependent and endothelium-independent vasodilatations were reduced significantly in both SHR and SHRSP. The aorta of SHR showed increased contraction reaction to both high potassium andα-receptor agonist. The aorta of SHRSPshowed potassium-induced contraction increased,but theα-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)]. Seventy three point three percent of SHRSPdied of stroke. SHRSPhad the most significant intima inflammation and necrosis,with aneurysm formation and diffuse collagen fiber calcification in three layers of aorta(37.5%). No death,aneurysm or collagen calcification were found in WKY and SHR.Conclusions Severe hypertension can cause large vessel damages including vessel hyperplasia,inflammation,necrosis,collagen calcification,and endothelium/smooth muscle dysfunction. Concomitant hyper-nsulinemia may also accelerate vessel hyperplasia in hereditary hypertension.更多还原