缺锌对衰老大鼠海马精氨酸加压素水平的影响

采用Y－迷宫实验、放射免疫分析和原子吸收分光光反法，测定缺锌、衰老和正常Wistar大鼠学习记忆行为、海马AVP水平和血浆Zn含量变化。结果：与对照组相比，老龄和缺锌大鼠在Y－迷宫中达到学会标准所需的潜伏期或次数明显延长（P＜0．05），血浆Zn和海马AVP水平明显降低（P＜0．05或P＜0.01）．提示表老过程中海马AVP水平明显降低，触发这种变化的原因可能与衰老过程中机体Zn水平的降低有关。     

精氨酸血管加压素与心力衰竭研究的进展

众所周知,神经激素异常与充血性心力衰竭的病理生理密切相关。改善充血性心力衰竭预后的成功方法主要是阻断神经激素系统的激活。肾素-血管紧张素-醛固酮系统和交感神经系统的拮抗剂和阻断剂显著改善了充血性心力衰竭患者的预后。心力衰竭时过量分泌的精氨酸血管加压素可能加速充血性心力衰竭的病理进程。精氨酸血管加压素受体拮抗剂阻断精氨酸血管加压素的作用,是一种治疗充血性心力衰竭的新方法,可能使患者获益。     

血浆尾加压素与高血压、心肌肥厚和血管重构关系的研究

目的:观察原发性高血压、高血压合并心肌肥厚及血管重构患者血浆尾加压素Ⅱ(urotensinⅡ,UⅡ)含量的变化,探讨UⅡ在高血压病发生发展过程中的意义。方法:选择原发性高血压患者67例(高血压组),和正常人34例(正常对照组),应用超声方法检测颈动脉内-中膜厚度(IMT)、左室重量指数(LVMI),并将原发性高血压患者分为单纯性高血压组,高血压合并血管重构组及合并心肌肥厚组,采用放射免疫分析法检测血浆UⅡ含量。结果:高血压组患者血浆UⅡ含量(5.14±2.59)pg/ml,明显低于正常对照组(6.75±1.55)pg/ml及单纯性高血压组(6.54±2.00)pg/ml,P<0.01。而单纯性高血压组与正常对照组比较无显著差异,P<0.05。较之正常对照组,血管重构组患者IMT,心肌肥厚组患者LVMI、IMT明显增加;这两组血浆UⅡ含量明显减少,亦明显少于单纯性高血压组,分别为(5.08±2.47)pg/ml,P<0.05;(3.85±1.97)pg/ml,P<0.05;并且血浆UⅡ水平与IMT、LVMI呈显著的负相关(分别为r=-0.506,P<0.01;r=-0.399,P<0.01)。结论:UⅡ可能在高血压病血管重构及心肌肥厚的过程中有重要作用,但作用机制及其意义有待深入研究。     

大鼠钙化血管尾加压素Ⅱ及其受体上调

目的 观察血管钙化大鼠主动脉和心肌尾加压素Ⅱ及其受体表达的变化.方法 采用维生素D3 和尼古丁诱导大鼠血管钙化模型,以Von Konsa染色检测血管钙化,以原子吸收法和磷酸苯二钠法测定血管钙含量和碱性磷酸酶活性,放射免疫法检测血浆、主动脉和心肌尾加压素Ⅱ含量,免疫组织化学法检测血管尾加压素Ⅱ的表达,RT-PCR法检测主动脉和心肌尾加压素受体mRNA水平.结果 维生素D3 和尼古丁能够诱导大鼠典型血管钙化形成.Von Kossa染色可见血管钙化大鼠主动脉有大量黑色颗粒沉淀,血管钙含量、碱性磷酸酶活性明显升高,主动脉尾加压素Ⅱ含量、主动脉和心肌尾加压素受体基因表达明显上调.精氨酸饮食能减轻血管钙化,血管钙含量、尾加压素Ⅱ水平及尾加压素受体mRNA表达与单纯钙化组相比轻度下降,但无统计学意义.蛋氨酸饮食能加重血管钙化,增加钙含量,上调尾加压素Ⅱ表达,降低碱性磷酸酶活性.各组之间血浆尾加压素Ⅱ水平差异无统计学意义.结论 大鼠钙化血管尾加压素Ⅱ表达上调,提示尾加压素Ⅱ可能参与了血管钙化的发展过程.     

精氨酸加压素诱导大鼠心脏成纤维细胞胶原合成的作用

目的 :探讨精氨酸加压素 （AVP）对大鼠心脏成纤维细胞 （CFs）胶原合成的影响。方法 :采用胰酶消化法分离、培养新生 SD大鼠 CFs,3H-脯氨酸掺入法和羟脯氨酸比色法分别观察不同浓度 AVP及其 V1 受体拮抗剂 [d（CH2 ） 5 Tyr2 （Me） ]AVP对 CFs的影响。结果 :1CFs3H-脯氨酸掺入率随着 AVP浓度的增加而增高 ,其中 10 - 7mol/ L,10 - 6 mol/ L AVP组的 3H-脯氨酸掺入率分别为 （5 41± 96 ） cpm/ 5 0 0 0 cells和 （5 6 5± 72 ） cpm/ 5 0 0 0 cells,较对照组 （16 6± 31） cpm/ 5 0 0 0 cells明显增高 （均 P<0 .0 1） ;10 - 7m ol/ L AVP+ 10 - 7mol/ L[d（CH2 ） 5 Tyr2 （Me） ]AVP组3H -脯氨酸掺入率 （2 6 8± 6 4） cpm/ 5 0 0 0 cells较 10 - 7m ol/ L AVP组明显降低 （P<0 .0 1）。 2 CFs培养上清光吸收值（A值 ）随着 AVP浓度的增加而增高 ,其中 10 - 7m ol/ L ,10 - 6 m ol/ L AVP组的培养上清 A值分别为 0 .2 2± 0 .0 1和0 . 2 4± 0 .0 1,明显高于对照组 0 .2 0± 0 .0 1,有统计学意义 （均 P <0 .0 1） ;10 - 7m ol/ L AVP+ 10 - 7mol/ L [d（CH2 ） 5 Tyr2 （Me） ]AVP组的 A值为 0 .19± 0 .0 1,明显低于 10 - 7mol/ L AVP组 （P<0 .0 1）。结论 :AVP促进 SD大鼠 CFs胶原合成 ,其作用可能与 V1 受体介导有关     

慢性心力衰竭伴低钠血症患者血浆血管加压素和脑钠肽水平的变化

目的:探讨血管加压素(AVP)、脑钠肽(BNP)在慢性心力衰竭伴低钠血症发生发展过程中的作用.方法:用放射免疫法同时测定77例慢性心力衰竭患者(心力衰竭组),包括34例伴低钠血症慢性心力衰竭患者和43例正常血钠的慢性心力衰竭患者以及36例健康志愿者(正常对照组)血浆AVP、BNP水平.结果:两组心力衰竭患者血浆AVP、BNP水平均较正常对照组升高,伴低钠血症心力衰竭患者升高更为显著.随心功能级别增高,血浆AVP、BNP水平升高更明显.血浆AVP与BNP水平呈显著正相关(r=0.515,P＜0.001),而血浆AVP、BNP水平越高,血钠越低,呈显著负相关(分别为r=-0.403,P＜0.001;r=-0.394,P＜0.001).结论:心力衰竭患者血浆AVP、BNP分泌明显异常,AVP、BNP分泌增加可能是导致心力衰竭低钠血症的重要原因之一,在低钠血症发生中两者可能为协同作用.     

健康大鼠血管衰老性重塑与血管衰老相关基因的关系

目的通过研究健康大鼠血管衰老性重塑形态学变化及衰老相关基因表达,探讨血管衰老性重塑可能的分子调控机制,为临床有效干预血管衰老提供分子靶点。方法观察主动脉组织形态及内皮细胞显微结构变化,应用Western blotting分析4、10、16月和24月龄大鼠血管重塑p16INK4a和p21cip1蛋白表达变化。结果随增龄,大鼠主动脉管壁增厚,纤维化程度增高,内皮细胞形态呈现衰老改变,p16INK4a和p21cip1蛋白表达呈时间依赖性上调。结论血管衰老性重塑的分子机制之一可能与上调细胞周期蛋白p16INK4a和p21cip1的表达有关。进一步阐明其调控机制可为延缓血管衰老,防治动脉粥样硬化提供理论依据。     

血管加压素受体拮抗剂临床研究的现状及展望

传统治疗等容性或高容量性低钠血症的方法包括限水、应用高渗盐水及去甲金霉素等,但均有明显的副作用,导致其临床应用受限.血管加压素受体拮抗剂(VRAs)主要通过阻断过度产生的(精氨酸加压素)AVP,使净水(非溶质水)排出增加,达到升高血浆渗透压的作用已被美国食品药品管理局(FDA)批准用于治疗等容性低钠血症.对此类药物的进一步研究发现VRAs还可用于治疗由于AVP受体变异导致的肾源性糖尿病(NDI),甚至可能延缓多囊肾的进展.本文对于目前国内外非肽类VRAs药物的研究情况进行综述,并进一步探讨其潜在的临床使用价值.     

卡维地洛对急性心肌梗死大鼠血流动力学和心肌胶原含量的影响

目的研究卡维地洛(Carvedilol)对大鼠急性心肌梗死(AMI)后血流动力学的影响及其与心肌组织中胶原含量的关系。方法23只AMI术后存活的雄性SD大鼠随机分为AMI对照组(n=11)和卡维地洛治疗(Carvedilol)组(n=12),另设假手术组(n=11)。给药6周后测量室间隔超声背向散射参数(平均背向散射积分标化值IBS%,背向散射积分周期变化值CVIB)及血流动力学参数、心功能指标。结果(1)与假手术组相比,AMI组大鼠SBP、DBP、LVSP及±dp/dtmax及其校正值(±dp/dtmax/LVSP)均显著降低,LVEDP显著增高,高频超声检测显示IBS%显著升高,CVIB显著降低(均为P<0.05)。(2)与AMI组相比,Carvedilol治疗组大鼠SBP、DBP及LVSP均未进一步降低(P>0.05),LVEDP显著降低,±dp/dtmax及其校正值(±dp/dtmax/LVSP)显著升高,高频超声检测显示IBS%显著降低,CVIB显著升高(均P<0.05)。结论第3代β受体阻滞剂Carvedilol的干预有助于恢复AMI大鼠受损的左室功能,这可能与其抑制非梗死区心肌胶原过度沉积有关。     

自发高血压大鼠左心室心肌胶原含量与舒张功能的相关性研究

目的测定自发高血压大鼠(SHR)左心室心肌胶原含量和舒张功能的参数,探讨二者的相关性,并揭示它们的增龄性改变。方法雄性SHR共30只(8、14周和20周各8只,32周6只),行组织多普勒成像(TDI)检测左心室舒张功能。处死后取左心室心肌,用羟脯氨酸试剂盒测定羟脯氨酸含量;反转录-聚合酶链反应(RT-PCR)检测Ⅰ型和Ⅲ型胶原的mRNA表达。结果 TDI显示,二尖瓣环舒张早期速度(Ea)随增龄减低(P0.05),二尖瓣环舒张早期与晚期速度比值(Ea/Aa)32周比8周时减低(P0.01),左心室等容舒张时间(TVRT)随增龄延长(P0.05),Tei指数随增龄增加(P0.05)。心肌羟脯氨酸含量、Ⅰ型和Ⅲ型胶原的mRNA表达随增龄均增加(均为P0.05)。羟脯氨酸含量、Ⅰ型和Ⅲ型胶原mRNA表达与TDI指标Ea、Ea/Aa均早负相关(r=-0.713～-0.431,P0.001～0.05),与IVRT均呈正相关(r=0.427～0.721,P0.001～0.01),与Tei指数均呈正相关(r=0.413～0.576,P0.001～0.01)。结论 SHR左心室心肌胶原含量呈增龄性增加,舒张功能呈增龄性降低,二者具有相关性。     

Changes in ECG,plasma and myocardial lipids in experimental myocardial hypertrophy in rats

Summary ECG, systolic blood pressure (BP), the ratio (R) of grams of myocardial mass/100 g of body mass, total lipids, cholesterol, triglycerides and phospholipids in blood plasma and the left ventricular myocardium, as well as the plasma free fatty acids, were investigated in 58 male Wistar rats 3,30 and 180 days after operation, in a model of myocardial hypertrophy (MH) induced by experimental coarctation hypertension, after the method of Sclye.An attempt was made to correlate some functional and metabolic indices which characterize the development of this type of MH. On a background of progressively rising BP and parallel increasing R, ECG change were recorded. They were typical of the respective stage of arterial hypertension and MH and expressed mostly in a shifting of the electrical axis of the heart to the left and in essential repolarization disturbances. The most significant changes in the studied lipid fractions were found 30 days after the induction of hypertension. The pathological changes manifested on the 180th day are discussed in relation to age, the stage of hypertension and especially in relation to the developing hypoxic and ischaemic myocardial damage.     

Correlation of cellular changes and spatial memory during aging in rats

We describe neuronal density, neuroplasticity and vascular remodelling and their association with spatial memory in young (4-6 months), middle-aged (9-11 months) and aged (18-20 months) rats of both genders. The neuronal density was reduced in the hippocampus of middle-aged and aged rats, particularly in male rats. However the loss of spatial memory investigated using the Morris water maze, T-maze and 8-radial arm maze tests was found only in the aged groups. The data suggested a pre-symptomatic period of pathological brain aging. Surprisingly, the middle-aged groups showed an elevation of glutamate-decarboxylase immunoreactive neurons in the hippocampus and the striatum, an increase of dopamine output in the striatum and enhanced vascular remodelling in the hippocampus when compared with the young and, in some cases, aged groups. Together, the data suggest that the loss of neurons during midlife may stimulate and enhance neuronal plasticity and vascular remodelling. These compensatory responses to initial neuronal degeneration may play a role in delaying impending memory loss during the pre-symptomatic period of pathological brain aging.     

Ultrastructural changes in the endothelium of lung capillaries during experimental pneumonia

In 35 guinea pigs a model of pneumonia was produced by transtracheal introduction of a sterile string. Electron microscopic study revealed that in the early stage of pneumonia (3-14 days after onset) endothelial cells in the capillaries of alveolar walls develop changes aimed at intensification of their function in sustaining an enhanced transcapillary gas exchange. In the following stage (1-4 months) endothelial cells develop progressing dystrophic changes leading to structural and functional disturbance of the blood-oxygen barrier. The dystrophic changes in endothelial cells develop later than those in alveolar epithelium.     

Massive plasma arginine vasopressin (AVP) removal during hemofiltration stimulates AVP secretion in humans

Arginine vasopressin (AVP) was measured in the plasma and its ultrafiltrate in 11 patients with end-stage renal failure treated by hemofiltration. Nineteen liters of ultrafiltrate were produced in 170 min and continuously replaced by an isoosmotic substitution fluid to maintain constant body weight. Plasma and ultrafiltrate AVP concentrations were not significantly different and did not change with time. The AVP clearance rate due to hemofiltration was 114 +/- 2.6 (+/- SE) ml/min, which represented more than two thirds of the predicted MCR in these patients. Corrected plasma osmolality, body weight, mean blood pressure, hematocrit, and PRA did not change during the hemofiltration session. These results indicate that there is a compensatory increase in AVP production which maintains plasma AVP unchanged in response to the increased MCR resulting from hemofiltration. The responsible stimulus could be a direct effect of the decrease in plasma AVP on the AVP-secreting neurones. Alternatively, ultrafiltration itself, via the hemodynamic changes it produces or the loss of an unrecognized inhibitory substance, may be the stimulus to AVP secretion.     

Unexpected changes in the catecholamine content of platelets and plasma during exercise

Catecholamines are retained within platelets for several hours after plasma catecholamine concentrations have returned to baseline. To determine whether platelet catecholamine concentrations may provide an index of short-term elevations in plasma adrenaline (A) and noradrenaline (NA), the response of plasma and platelet catecholamines to an interval supramaximal, Max (107% VO(2) Max), and submaximal, Submax (37% VO(2) Max), cycling protocol was examined in seven healthy male volunteers, 22-34 years. Despite large rises in plasma NA and A in the Max study (12- and 8-fold increases above baseline, respectively) and smaller rises in the Submax study, the baseline platelet concentrations of A and NA fell significantly in the first 15 min of exercise in both groups. This fall was greater in the SubMax protocol. Catecholamine concentrations then increased slowly in the second half of exercise, but never returned to baseline. The circulating platelet count almost doubled during the exercise period, increasing from 308 to 569 X 10(3) platelets/ml plasma in both studies, returning close to baseline in recovery. These results indicate that at the beginning of exercise there is large rise in plasma catecholamines and the circulating platelet count, with a fall in the platelet catecholamine concentrations. This suggests that a sequestered platelet population, free of catecholamines, is released at the beginning of exercise. This release most probably occurs from the spleen. If this is the case, the reason for a propagation of platelets in the spleen, free of catecholamines, requires further investigation.     

Unexpected changes in the catecholamine content of platelets and plasma during exercise

Catecholamines are retained within platelets for several hours after plasma catecholamine concentrations have returned to baseline. To determine whether platelet catecholamine concentrations may provide an index of short-term elevations in plasma adrenaline (A) and noradrenaline (NA), the response of plasma and platelet catecholamines to an interval supramaximal, Max (107% VO 2 Max), and submaximal, Submax (37% VO 2 Max), cycling protocol was examined in seven healthy male volunteers, 22-34 years. Despite large rises in plasma NA and A in the Max study (12- and 8-fold increases above baseline, respectively) and smaller rises in the Submax study, the baseline platelet concentrations of A and NA fell significantly in the first 15 min of exercise in both groups. This fall was greater in the SubMax protocol. Catecholamine concentrations then increased slowly in the second half of exercise, but never returned to baseline. The circulating platelet count almost doubled during the exercise period, increasing from 308 to 569 X 103 platelets/ml plasma in both studies, returning close to baseline in recovery. These results indicate that at the beginning of exercise there is large rise in plasma catecholamines and the circulating platelet count, with a fall in the platelet catecholamine concentrations. This suggests that a sequestered platelet population, free of catecholamines, is released at the beginning of exercise. This release most probably occurs from the spleen. If this is the case, the reason for a propagation of platelets in the spleen, free of catecholamines, requires further investigation.     

不同年龄大鼠组织NO含量和NOS活性的变化与衰老之间的关系

目的探讨组织一氧化氮（ＮＯ）含量与一氧化氮合酶（ＮＯＳ）活性的变化规律,揭示其与衰老的关系。方法采用铜离子活化镉还原法、硫代巴比妥酸染色法和血红蛋白氧化测定组织ＮＯ、丙二醛（ＭＤＡ）含量和ＮＯＳ的活性。结果与青年鼠组（４－５月龄相比,老年鼠组（２０－２２月龄）心脑肾组织ＮＯ降低差异显著性（Ｐ〈０．０１）,而中年鼠组（９－１０月龄）仅肾组织ＮＯ含量降低有显著性差异（Ｐ〈０．０５）。中年鼠组比较,老年