国产血管生成素对微血管稀少及血管内皮细胞作用

本研究旨在研究国产血管生成素对微血管稀少和血管内皮细胞的作用。观察对象为WKY鼠5周龄组、8周龄组、13周龄组和血管生成素治疗组。观察指标为微动脉A2、A3和A4。研究结果提示血管生成素可以预防微血管稀少并延缓靶器官细胞损害。     

盐酸莫索尼定对自发性高血压大鼠左室肥厚的影响

目的:研究国产盐酸莫索尼定对自发性高血压大鼠左室肥厚时心肌纤维化和冠状动脉微血管结构的影响。方法:20周龄的雄性自发性高血压大鼠30只随机分为①Mox+SHR组;②Cap+SHR组;③SHR组, 每组10只。另设性别周龄相配的SD大鼠10只为正常对照组(NC组)。观察13周后处死动物, 获取心脏。测量左心室重/体重, 左室胶原分数, 标准化血管周胶原面积和肌间动脉中膜厚度的变化。结果:Mox+SHR组不仅左心室重/体重明显低于SHR组, 而且左室胶原分数低于SHR组(0.086±0.018vs0.046±0.015, P＜0.01), 血管外膜胶原少于SHR组(0.69±0.11vs1.34±0.29, P＜0.01), 中膜薄于SHR组。结论:盐酸莫索尼定长期抗高血压治疗能够减轻左室肥厚时的心肌纤维化和改善受损的冠脉微血管结构。     

短链酰基辅酶A脱氢酶在大鼠心脏发育中的表达及其与心肌肥厚的关系

 目的：研究大鼠心脏发育过程中短链酰基辅酶A脱氢酶(short-chain acyl-CoA dehydrogenase, SCAD)的表达变化规律,并探讨其与高血压大鼠心肌肥厚的关系。方法：观察不同时期Wistar大鼠和不同周龄自发性高血压大鼠心肌组织的SCAD蛋白表达及酶活性变化,检测大鼠的血清和心肌游离脂肪酸含量。结果：与胚胎期19 d Wistar大鼠组比较,出生后1 d、2周、6周及16周龄Wistar大鼠组心肌的SCAD蛋白表达及酶活性增加,血清和心肌游离脂肪酸含量明显减少,二者之间呈负相关,其中,从2周龄Wistar大鼠组开始差异有统计学意义。与周龄匹配的WKY大鼠组比较,2周龄自发性高血压大鼠组收缩压尚未升高,6周龄及16周龄自发性高血压大鼠组收缩压显著增高;各时点自发性高血压大鼠组的左室重量指数均明显增高,提示自发性高血压大鼠在血压升高之前,已经发生了明显的心肌肥厚。与周龄匹配的WKY大鼠组比较,2周、6周及16周龄自发性高血压大鼠组心肌的SCAD蛋白表达及酶活性明显下降,血清和心肌游离脂肪酸含量明显增加,呈显著负相关。结论：(1)SCAD蛋白表达随大鼠心脏的生长发育逐渐上调,可能与心脏对脂肪酸的利用增加密切相关。(2)SCAD的蛋白表达及其酶活性显著下降, 可能是导致自发性高血压大鼠肥厚心肌能量代谢“胚胎型再演”的分子基础。     

自发性高血压大鼠FXYD5基因表达的时空分布

目的:研究大鼠FXYD5(FXYD domain-containing ion transport regulator 5)基因表达在自发性高血压大鼠（SHR）及正常血压大鼠（Wistar-Kyoto, WKY）的时间与空间分布差异。方法:取4周、8周、13周及21周龄SHR的肾脏、肝脏、肠系膜二、三级动脉分支、大脑和心脏组织，以同周龄WKY作对照，采用Northern blotting方法分析FXYD5mRNA表达丰度。结果:Northern blotting的结果显示：13周、21周龄SHR的肾脏组织FXYD5基因表达丰度较同周龄WKY低；在肺组织，除8周龄该基因的表达水平在SHR组略低于对照组外，其它周龄两组没有差别。结论:FXYD5基因在SHR中有着特异性的组织分布特点，并且在不同周龄的SHR， FXYD5基因在肾脏的表达水平不是恒定不变的，在时间上呈一钟形变化。提示FXYD5基因可能是一个高血压相关的基因，可能与高血压的发病有关。     

血管紧张素Ⅱ受体拮抗剂对高血压肾小动脉重建的影响

目的:研究血管紧张素II(AngII)受体拮抗剂对高血压肾小动脉重建的影响。方法:18只4周龄雄性大鼠分为:正常血压大鼠(WKY)组、自发性高血压大鼠(SHR)组、SHR口服losartan组,均饲养至16周。在肾组织切片上分别用光镜和电镜配合计算机图像分析法观测肾组织内小动脉的几何形态学指标和小动脉平滑肌及其间隙,离体肾脏灌流法测定最小肾血管阻力。结果:Losartan组的尾动脉收缩压、肾小动脉壁厚、壁面积、壁厚内径比和中层血管平滑肌细胞宽度以及最小肾血管阻力,均显著低于高血压对照组。结论:AngII受体拮抗剂losartan能预防SHR肾小动脉的重建。     

激光多普勒血流探测仪小波分析早期高血压大鼠血流灌注频谱特征

目的:利用高效激光多普勒血流探测仪(LDF)的小波分析早期自发性高血压大鼠(SHR)微循环血流灌注频谱特征。方法:8周龄、10周龄、13周龄雄性SHR大鼠(实验组)和8周龄、10周龄、13周龄WKY大鼠(对照组),每组各周龄大鼠均7只,采用多功能LDF检测两组大鼠耳、趾、脑皮质和肾皮质血流量(Flu),并利用小波分析上述部位的血流灌注信号(SFBO)的频谱特征。结果:13周龄实验组大鼠的趾部血流灌注信号在神经活动(brand4)和内皮来源(brand5)相关的信号区间内明显高于同周龄对照组大鼠(P0.05)。实验组大鼠各部位的血流灌注信号随年龄变化的趋势不明显,在趾部,10周龄实验组大鼠在各个频率信号区间的血流灌注信号均明显减弱,但是在13周时又再次升高,肾部交感神经来源(brand4)信号区间也呈现该现象。耳部和脑部的血流灌注信号随周龄的变化相对平稳。对照大鼠脑部的血流随着周龄的增加在各个频率区间都呈现血流灌注信号减弱的趋势,尤其是与内皮来源(Brand5)(P0.05或P0.01)和肌源性活动(Brand3)相关的频率范围。结论:通过小波转换分析早期高血压大鼠的激光多普勒血流灌注信号,从时频分析的角度为评估高血压大鼠的微循环状况提供另一个方向。     

自发性高血压鼠的微血管稀少与靶器官损害

自发性高血压鼠的微血管稀少与靶器官损害江时森＊顾小萍＊李辉＊传统观念认为高血压对靶器官损害发生在后期，并且与血压呈正相关。晚近研究表明高血压早期就可以有靶器官受损表现［１］，微循环的功能和结构状态与靶器官损害程度密切相关［２］。本研究旨在观察微血管稀...     

阿托伐他汀对自发性高血压大鼠心肌组织PPARs表达的影响

目的： 探讨阿托伐他汀对自发性高血压大鼠心肌组织PPARs（peroxisome proliferator-activated receptors, PPARs）表达的影响及其对心肌肥厚的逆转作用与可能机制。方法: 自发性高血压大鼠分为阿托伐他汀灌胃治疗组（SHR-A，30 mg·kg-1·d-1）及模型组（SHR），治疗8周，同周龄Wistar-Kyoto 鼠为正常血压对照组。治疗前及治疗后2、4、8周测量大鼠尾动脉血压。治疗后测血浆血脂水平，以心脏组织病理分析判断心肌肥厚，Western blotting 检测心肌组织PPARα、PPARγ的表达水平。结果: 经过8周治疗， SHR-A组及SHR组血压及血脂水平无明显差异（P＞0.05）。SHR-A组左室重量指数低于SHR组（P＜0.01）。在SHR-A组，PPARα及PPARγ表达高于SHR组（P＜0.01）。结论: 阿托伐他汀显著改善自发性高血压大鼠心肌组织PPARs表达，有效逆转左室肥厚，可能与其降压及降脂作用无关。     

自发性高血压鼠脑底动脉降钙素基因相关肽能神经纤维的分布

应用免疫组织化学ABC法和神经交点计数技术,观察了10只自发性高血压大鼠和10只正常血压大鼠脑底动脉降钙素基因相关肽(CGRP)能神经纤维的分布。结果证明:在自发性高血压鼠的大脑前动脉、大脑中动脉、大脑后动脉和基底动脉壁上均可见CGRP免疫反应阳性纤维,纤维呈细曲线状,多呈网状走行;与正常血压鼠脑底血管同名动脉比较,其密度明显减少。正常血压鼠脑底血管CGRP能神经纤维多呈环形走行。高血压鼠的CGRP能神经纤维的分布随着高血压的发生而明显减少,提示CGRP能神经纤维的减少与高血压的发生、发展具有一定的关系。     

苯丙氨酸缓解高血压大鼠血管重塑

目的：应用激光共聚焦显微镜观察高血压时血管重塑，以及苯丙氨酸治疗后对血管重塑的影响。方法： 以Wistar-Kyoto 大鼠 (WKY)和自发性高血压大鼠(SHR)为研究对象，采用固定压力灌注和荧光染色激光共聚焦显微镜观察分析肠系膜小动脉的管腔、厚度和血管平滑肌的排列方向。结果： SHR较WKY 管腔缩小，管壁增厚，同时血管平滑肌排列方向紊乱。应用苯丙氨酸治疗后，管腔扩大，管壁变薄，血管平滑肌排列方向改善。结论： 高血压大鼠肠系膜小动脉存在血管重塑现象，苯丙氨酸可以改善血管重塑。     

阿托伐他汀对自发性高血压大鼠细胞色素P450羟化酶基因表达的影响

目的： 评价阿托伐他汀对自发性高血压大鼠（SHR）血压和细胞色素P450羟化酶(CYP)4A1的调节作用。方法： 18只SHR随机分为3组：SHR对照组、阿托伐他汀50 mg组(HATV组)和10 mg组(LATV组)；6只Wistar-Kyoto大鼠(WKY)作为正常对照组。给药共10周,分别于给药前和给药后每2周测量大鼠尾动脉收缩压(SBP)；RT-PCR、Western blotting法检测心、肝、肾及主动脉中CYP4A1 mRNA和蛋白质表达；并测定血脂含量。结果： 用药前SHR各组SBP均显著高于WKY组(P<0.01)；HATV组在给药后第6、8、10周和LATV组在给药后第10周SBP明显低于SHR对照组(P<0.05或P<0.01)。在CYP4A1 mRNA及其蛋白质表达中，SHR对照组4种组织均明显高于WKY组(P<0.01或P<0.05)；给药10周后，HATV组心、肾及主动脉和LATV组肾和主动脉的表达均明显低于SHR对照组(P<0.01或P<0.05)；同时，用药2组血脂水平亦明显低于SHR对照组(P<0.01或 P<0.05)。结论： 阿托伐他汀可下调CYP4A1基因的表达，这可能是其降低血压的作用机制之一。     

RNA阵列技术检测自发性高血压大鼠甲羟戊酸途径酶的基因表达

目的：探讨甲羟戊酸(MVA)途径的9个酶在不同周龄自发性高血压大鼠(SHR)发病过程中的基因表达变化特点。方法:提取2、4、6、8、10、12不同周龄雄性SHR以及正常血压大鼠(WKY)的心室肌、血管平滑肌、肝脏和肾脏4种组织的总RNA，共294个样品，利用高通量RNA阵列技术(RNA array)检测甲羟戊酸途径的9个酶的基因在不同周龄SHR和WKY大鼠中mRNA表达谱的改变。 结果:（1）SHR大鼠从第6周开始收缩压明显高于WKY(P<0.01)。 （2）12周龄SHR大鼠体内血清胆固醇浓度明显低于WKY大鼠，组织中的胆固醇浓度没有明显差异(P<0.01)。（3）在SHR大鼠心脏、血管、肝脏、肾脏组织中：MVA中间产物的合成酶如法呢醇焦磷酸合成酶(FDS)、异戊烯化焦磷酸化异构酶(IDI)、法呢醇转移酶α亚基(FT1)和β亚基(FT2)的表达明显高于WKY(P<0.01)。（4）SHR肾脏组织中羟甲基戊二酰辅酶A还原酶（HMGR）、甲羟戊酸激酶（MVK）、焦磷酸甲羟戊酸脱羧酶（MVD）、鲨烯合成酶（SQS）和鲨烯环氧化酶（SQ） 表达较为一致，早期(2-4 周)SHR大鼠的基因表达明显高于WKY，随着周龄增加SHR的表达进一步增高，且与WKY相比都有明显差异(P<0.01) 。（5）在心脏、血管和肝脏中，HMGR、MVK、MVD、SQS和SQ的基因表达无明显规律。结论:SHR大鼠随着周龄的增长甲羟戊酸途径中各酶基因表达的改变，以非胆固醇产物类合成酶(如IDI、FDS和FT1、FT2)表达增加为特点，这一改变是否与高血压有关尚待进一步验证。     

Are renal mechanisms involved in primary hypertension? Evidence from kidney transplantation studies in rats

Summary Previous renal transplantation experiments in genetically hypertensive and normotensive rat strains indicated that a genetic defect in the kidney may be primarily involved in the pathogenesis of primary hypertension. In order to investigate whether this is also true for the most widely used animal model of primary hypertension, the spontaneously hypertensive rat (SHR), we performed renal transplantations using SHR and normotensive Wistar-Kyoto rats (WKY) as kidney donors and bilaterally nephrectomized F1 hybrids, bred from SHR×WKY parents as renal graft recipients. Our studies were also designed to differentiate between primary and secondary renal mechanisms as a possible cause of posttransplantation hypertension. Recipients of renal grafts from adult, naive SHR but not from adult normotensive WKY kidney donors developed posttransplantation hypertension. Permanent blood pressure normalization by antihypertensive treatment in adult SHR kidney donors and prehypertensive, young age of SHR kidney donors reduced, but did not prevent, posttransplantation hypertension. Increasing renal perfusion pressure in WKY kidney donors (2-kidney 1-clip hypertension) also resulted in posttransplantation hypertension in recipients of the non-clipped kidneys. Blood pressure remained normal in recipients of renal grafts from young WKY kidney donors. These data suggest that SHR kidneys carry a genetic defect which may be primarily involved in the pathogenesis of primary hypertension.Abbreviations SHR spontaneously hypertensive rat - WKY Wistar-Kyoto rat Preprint of a lecture to be read at the 22nd Congress of the Gesellschaft für Nephrologie, Heidelberg, September 15–18, 1991 (Editor: Prof. Dr. E. Ritz, Heidelberg)     

Proximal-tubule-like epithelium in Bowman's capsule in spontaneously hypertensive rats. Changes with age.

Kidneys were samples from male spontaneously hypertensive rats (SHR) and normotensive rats (WKY) in four groups. Renal tissues were examined in 64 rats: 6 SHR and 6 WKY rats 8 and 16 weeks of age and 10 SHR and 10 WKY rats 32 and 64 weeks of age. Tissue samples were fixed, processed, and stained by routine histologic procedures. The parietal layer of Bowman''s capsule in 100-115 renal corpuscles from right to left kidney sections was classified as squamous or cuboidal epithelium. The cuboidal epithelium was similar in structure to that of the proximal tubule. Quantitative information from right and left kidneys was pooled, because the data did not differ significantly. The percentages of renal corpuscles with proximal tubule-like epithelium present at the parietal layer of Bowman''s capsule in the SHR was 13%, 35%, 44%, and 81% at 8, 16, 32, and 64 weeks, respectively. In WKY rats the values were 4%, 0.5%, 5%, and 13% at 8, 16, 32, and 64 weeks, respectively. The increase in the percentage of renal corpuscles with proximal tubule-like epithelium in SHR Bowman''s capsules suggest an association between this tissue and hypertension. The modified layer of Bowman''s capsule may be a response to an increase in blood pressure, may have some role in the etiology of hypertension, or may be irrelevant to hypertension.     

Myocardial cell growth and blood pressure development in neonatal spontaneously hypertensive rats

We evaluated the changing morphologic features of cardiac muscle cells (myocytes) and nuclei from neonatal spontaneously hypertensive rats (SHR) and their parent, normotensive strain Wistar Kyoto rats (WKY) and compared these with increasing heart weight and blood pressure development to determine if alterations in cell growth were present at this early stage of development. Femoral artery blood pressures were obtained from rats at 2 to 5-day intervals from birth to 21 days of age by using a micropipette servo-null pressure recording system. Tritiated thymidine autoradiography was used to study myocyte nuclear development, and isolated myocytes were prepared to evaluate cell-size changes by using a Coulter Counter system (Coulter Electronics, Hialeah, Florida). Heart weight and blood pressure were elevated in SHR when compared to WKY at birth. Myocytes were all mononucleated at birth in both strains and were of equal size, demonstrating that the larger heart mass in SHR was due to an increased number of cells. Heart weight relative to body weight remained greater in SHR when compared to WKY throughout the 28-day study period, but cell numbers became equal in the two strains by the 2nd week. A this time (6 to 9 days postpartum) blood pressure was also similar in both strains, but increased significantly again in SHR by 15 and 21 days of age. Cell maturation occurred earlier in SHR than in WKY as indicated by an earlier development of binucleate myocytes and there was an earlier initiation of hypertrophic myocyte growth in SHR. Increase in SHR cell size occurred at a time when blood pressures were not different, suggesting that greater cell size in SHR than in WKY was not due to differences in blood pressure. Therefore, when compared to the WKY, the SHR had three phases of altered cell growth: a first phase of accelerated hyperplastic growth during the fetal period, and a second phase (6 to 12 days of age) of earlier initiation of hypertrophic cell growth and increased myocyte size. The SHR myocyte changes in the second phase occurred while the SHR and the WKY blood pressures were not significantly different. Finally, in a third phase (at 15 days of age and over), SHR had a sustained increase in myocyte size as well as elevated blood pressure.     

Cardiac design and pressure-volume characteristics of the left ventricle in normotensive (WKY) and hypertensive (SHR) rats after various dietary sodium treatments

Normotensive (WKY) and hypertensive rats (SHR) from 5 to 13-14 weeks of age were given 'low' (LNa; 0.5 mmol Na 100 g-1 food), 'control' (CNa; 5 or 12 mmol), 'high' (HNa; 50 mmol) and in SHR also 'medium low' (mLNa; 2 mmol) and 'very high' (vHNa; 120 mmol) sodium diets, to explore how such 240-fold variations in Na intake affect cardiac design. This was assessed in isolated perfused, temporarily-arrested hearts by recordings of left ventricular (LV) diastolic pressure-volume relationships (P/V), LV and RV weights, and by calculations of the ratio between LV wall thickness and internal radius (w/ri), after in vivo recordings of awake mean arterial pressure (MAP) and heart rate (HR). In WKY, where MAP was the same in all diet groups, the HNa group showed an increased w/ri due to a 20% reduction of LV diastolic volume, with signs of reduced wall compliance compared with CNa. The LNa WKY showed less marked changes in the same direction. In the SHR LNa group, where MAP was lowered about 20 mmHg, LV diastolic volume was reduced nearly 20% at a modest w/ri increase, while HNa and Cna SHR had equal MAP, LV weights, P/V and w/ri relationships. However, in vHNa SHR, where MAP was elevated about 25 mmHg, the LV showed a mainly eccentric hypertrophy with 15% increase of diastolic volume at a slight increase of w/ri. These differentiated, and in WKY and SHR partially differing structural cardiac adaptations consequent to changes in Na intake, can hardly be ascribed only to the respective pre- and afterload alterations, suggesting that also altered neuro-hormonal profiles may have contributed with 'trophic' influences.(ABSTRACT TRUNCATED AT 250 WORDS)     

Morphological alterations in skeletal muscle of spontaneously hypertensive rats

The Extensor digitorum longus (EDL) and the soleus muscles of spontaneously hypertensive rats (SHR) were studied in comparison with those of their normal counterparts, the Wistar Kyoto (WKY) rats. Quantitative assessment of capillaries and muscle fibre typing was done with optical microscopy, while the study of capillary abnormalities was performed by ultrastructural observation. There were no differences in fibre type proportion or in capillarity indexes between the SHR and the control rats. A reduction in the area of IIB fibres was found in the EDL muscle of the hypertensive animals. The ultrastructural study showed abnormalities in the capillaries of both muscles in SHR, the cross section of the endothelial cells was enlarged; there was irregular distribution of caveolae and pinocytic vesicles, the capillary basement membrane showed irregular width, with parts engrossed and reduplicated. Some pericytes were prominent. There were macrophages present in the interstitial space. In some muscle fibres there was disorganization of the sarcomere structure, swelling of the sarcotubular system, abundant autophagic vacuoles, and proliferative satellite cells. There were abundant collagen fibrils. The presence of cellular rests, autophagic vacuoles and loss of sarcolemma indicated necrosis. It can be concluded, that in SHR, muscle capillaries showed alterations that may be the substrate of functional rarefaction, although anatomical rarefaction (number reduction) could not be demonstrated. In EDL and soleus muscles of SHR, signs of a mild myopathy with focal fibrosis were present.