自发性高血压大鼠主动脉弓重建的形态学研究

1、    自发性高血压大鼠主动脉弓重建的形态学研究*        【摘要】目的研究高血压动脉重建规律，为揭示高血压主动脉弓的血流动力学特点提供形态学基础。方法应用组织学和计算机像分析技术，对36例SHR和WKY大鼠(各分4周、16周和26周)主动脉弓进行定量形态学研究。结果随着年龄增长，大鼠主动脉弓形态和显微结构发生重建。高血压主动脉弓重建以壁厚、中膜厚、管壁面积、中膜面积和中膜厚内径比以及血管平滑肌、弹性纤维和胶原纤维等结构成分的相对含量显著增大为特征。结论SHR 成年以前

2、主动脉重建是年龄不断增长和血压逐步升高综合作用的结果，其中高血压是主要因素。大鼠主动脉弓形态结构在血管周向呈显著非均匀性，并在高血压重建中变得更为显著。【关键词】主动脉弓形态测量学显微结构高血压血管重建 MORPHOLOGICAL STUDY ON REMODELING OF THE AORTIC ARCH IN SPONTANEOUSLY HYPERTENSIVE RATSCai Guojun, Jiang Zonglai, Yang Xiangqun, Ji Kaihong(Department of Anatomy, Institute of Biomedical Engineering

3、, The Second Military Medical university, Shanghai)【Abstract】Objective To provide essential morphological data for research concerning biomechanics and hemodynamics of the vessel, and for further research on the law of vascular remodeling in hypertension,a morphological quantitative study was conduc

4、ted. MethodsThirty-six aortic arch specimens of SHR and WKY rats(divided into 4w, 16w and 26w groups respectively) were used. After fixation under 120mmHg (16kPa) pressure, the aortic arch was cross-sectioned at the sites proximal to the origin of the three branches.The sections were stained so as t

5、o reveal the elastin, collagen and smooth muscle, and then were analyzed by the computer image system. ResultsHypertension leads to increases in wall thickness, cross-sectional wall area, media:lumen ratio and relative area(Aa%) of elastin, collagen and smooth muscle in the aortic arch. The media th

6、ickness and Aa% of the microstructural components in different circumferential directions of the aortic arch are unequal significantly in SHR and WKY. ConclusionBefore adulthood, the remodeling of the aortic arch in SHR is a comprehensive effect of hypertension and aging, of which hypertension is mo

7、re important. The inequality of structure of the aortic arch exists all along during growth and the development of hypertension, and becomes more significant during the remodeling in hypertension.【Key words】 Aortic arch; Morphometry; Microstructure; Hypertension; Vascular remodeling高血压血管重建(remodelin

8、g)是高血压血管的适应性生长和基本病理改变，血管形态重建必然导致其力学性质及血管功能的改变。Owens1和Gohlke2等发现高血压时血管平滑肌、弹性纤维和胶原纤维等大量积聚。Hadjiisky3则认为主动脉中膜重建和血压升高导致的血管应力及应变的变化密切相关。主动脉弓是一段弯曲且分支的血管，研究其在高血压重建中的形态，对建立主动脉弓生物力学模型，进一步揭示高血压状态下主动脉弓的血流动力学特点有重要意义。目前这方面研究尚不多见，而高血压血管重建中主动脉弓结构的血管轴向和周向非均匀性尚未见报道。材料和方法1.动物与分组雄性自发性高血压大鼠(spontaneously hypertensive r

9、at, SHR)18只，按鼠龄4周(高血压前期)、16周(高血压形成期)和26周(高血压稳定期)分为3组，每组6只；雄性同龄同种系正常血压的京都种大鼠(Wistar-Kyoto rat, WKY)18只为对照组。2.取材和组织切片动物颈总动脉插管，测颈动脉收缩压。动物处死后，经胸主动脉远端插管，16kPa压力下灌注固定后，分离主动脉弓，垂直血管长轴，分别于升主动脉中段、主动脉弓3大分支起始处近端和胸主动脉起始处切断血管取材(1)。标记血管段方位，以血管弓凸缘为上，凹缘为下，在与上、下相垂直的方向上，近腹侧为前，近背侧为后。常规石蜡切片(厚3m)。    

10、1大鼠主动脉弓模式。示取材部位：A.升主动脉中段B.头臂动脉起始处近端C.左颈总动脉起始处近端D.左锁骨下动脉起始处近端E：胸主动脉起始处Fig.1 Diagram of the rat aortic arch, showing the special sections where measurements were taken:A, Middle point of the ascending aorta. B,Proximal to the origin of the innominate atery.C,Proximal to the origin of the left common c

11、arotid artery.D,Proximal to the origin of the left subclavian artery.E,Origin of the thoracic aorta.3.切片染色和像分析各血管段连续3张切片分别用Neubert酸性茜素蓝法、Weigert间苯二酚复红法和茜胺蓝法染血管平滑肌、弹性纤维和胶原纤维。光镜下用计算机像分析测定血管的形态指标。结果作统计学处理，两组资料比较用t检验，多组资料比较用方差分析。结果1.大鼠的血压SHR和WKY各组大鼠的颈动脉收缩压见2。    2各组大鼠的颈动脉收缩压*SHR与WKY相

12、比，P<0.01Fig.2Systolic pressure of carotid artery of SHR and WKY.?*P<0.01, SHR compared with WKY.     2.主动脉弓的几何形态学SHR与WKY主动脉几何形态指标随年龄均呈增长趋势(3)。16周和26周SHR与WKY比较，主动脉壁厚、壁面积和中膜厚内径值显著增大(4)。在血管周向，各年龄组SHR和WKY主动脉弓中膜厚均呈显著非均匀性(5)。    3各组大鼠主动脉弓(切面C)的各项几何形态指标。16周、26周

13、SHR的壁厚、中膜厚、管壁和中膜面积均显著大于WKY，P<0.01Fig.3 Line graphs show vessel area, diameter and thickness of the aortic arch (section C). The wall thickness, media thickness, cross-sectional wall area and media area of SHR(16week and 26week groups) are larger than that of WKY, significantly,P<0.01. ID,inner

14、 diameter; OD,outer diameter; LA,lumen area; WA,cross-sectional wall area; MA,media area; WT,wall thickness;MT,media thickness    4各年龄组SHR与WKY相应切片的比较。A.4周SHRB.16周SHRC.26周SHRD.4周WKYE.16周WKYF.26周WKY    5SHR主动脉弓切片，示血管中膜厚周向非均匀性。5A.切面C(4周) 5B.切面B(26周)S.上壁A.前壁I.下壁P.

15、后壁3.主动脉弓的显微结构成分在主动脉弓轴向，各切面中膜血管平滑肌、弹性纤维和胶原纤维的相对含量(Aa%)连续变化。在周向，各显微结构成分相对含量也是不均匀的(6)。16周和26周SHR主动脉中膜3种显微结构成分的相对含量均显著大于WKY(79)。    6各组大鼠主动脉弓(切面C)不同周向显微结构成分的相对含量(Aa%)。16周、26周SHR的Aa%在各周向均显著大于WKY，各组大鼠3种显微结构成分的Aa%在血管周向均呈显著非均匀性，P<0.05。Fig.6 The relative area(Aa%) of elastin, collagen

16、and smooth muscle in different circumferential directions of the aortic arch(section C). The Aa% of elastin, collagen and smooth muscle are unequal in circumferential directions of the aortic arch in all groups, and in SHR of 16w and 26w groups, are significantly larger than that of WKY (P<0.05).

17、    716周SHR与WKY主动脉切面E的血管平滑肌。A.SHRB.WKYNeubert酸性茜素蓝染色×40    816周SHR与WKY主动脉切面A的弹性纤维。A.SHRB.WKYWeigert间苯二酚复红染色×40    926周SHR与WKY主动脉切面E的胶原纤维。A.SHRB.WKY苯胺蓝染色×40讨论1.高血压主动脉弓的重建SHR在4周以前血压基本正常，主动脉弓形态结构与WKY无明显差异，之后血压随年龄逐渐增长，至26周维持在26.7

18、kPa左右，此时SHR与WKY相比，壁面积、壁厚、中膜厚内径以及平滑肌、弹性纤维和胶原纤维的相对含量均显著增大。随年龄增长，大鼠主动脉弓形态和显微结构也发生重建，从16周到26周，WKY年龄性重建已明显减缓，而SHR由于血压仍持续升高，血管重建非常显著，可见，在成年以前，SHR主动脉重建是年龄不断增长和血压逐步升高综合作用的结果，其中，高血压是主要因素。2.力学因素在高血压动脉重建中的作用及对主动脉弓结构非均匀性的影响在生理情况下，血管的生长和消蚀保持一种动态平衡，血管在形态上保持稳定性，这与血管应力、应变的稳定性密切相关。高血压时，血管壁周向和轴向应力增加，应力和生长的平衡关系被打破，引起血

19、管平滑肌和纤维结缔组织的过度生长，管壁增厚4。力学因素在主动脉弓结构非均匀性的重建中也发挥关键作用。在血管周向，主动脉弓上壁中膜厚和显微结构成分相对含量显著大于下壁，这种结构非均匀性在正常和高血压大鼠中普遍存在，在正常人主动脉弓的研究中也发现类似规律，反映主动脉弓应力、应变的不均匀，与其血流动力学特点相关。根据Fung5“应力-生长法则”，可以得出如下推论：在动态平衡状态下，所有胶原纤维具有同一应力，所有弹性纤维具有另一均匀应力，在平滑肌细胞中所有致密体具有同样的空隙。那么，在血管高应力区，势必有更多的结构成分去承担某一均匀应力。SHR在血压升高过程中，主动脉弓上壁血管平滑肌、弹性纤维和胶原纤

20、维相对含量的增长率比下壁显著大(6)，即上壁的重建显著大于下壁，表明主动脉弓结构的周向非均匀性，在高血压重建中变得更为显著。这是由于血压升高，血流在主动脉弓弯曲分支的管道内离心作用加大，高速轴向血流移向血管上壁和分支处附近，进而形成螺旋形的二次流6，主动脉弓上壁附加压力增大，上壁增生重建明显，而下壁相对血流缓，应力低，重建生长慢。* 国家自然科学基金资助项目(No.19672072) Department of Anatomy, Institute of Biomedical Engineering, The Second Military Medical University, Shanghai 200433,China作者单位：第二军医大学解剖学教研室，生物医学工程研究所，上海200433参考文献1Owens GK, Reidy MA. Hyperplastic growth response of vascular smooth muscle cells following induction of acute hypertension in rats by ao