Costache G, Popov D, Georgescu A, Cenuse M, Jinga V V, Simionescu M
Institute of Cellular Biology and Pathology Nicolac Simionescu, Bucharest, Romania.
J Submicrosc Cytol Pathol. 2000 Jan;32(1):47-58.
The experimental model of Golden Syrian hamster subjected to concomitant hyperlipemia (diet-induced) and diabetes (by streptozotocin injection) for 24 weeks is characterised by the prevalence of micro- and macroangiopathies. We have used the hyperlipemic-diabetic (HD) hamsters to investigate: a) whether there is an alteration in the reactivity of the resistance arteries (mean internal diameter: 210-250 microm), b) if present, which are the structural and biochemical changes that accompany the functional modifications, and c) to examine the pathomorphological changes induced by the association of hyperlipemia and diabetes on vital organs such as myocardium and kidney glomeruli. To these aims, biochemical assays of plasma components, light- and electronmicroscopy, myographic, morphometric and spectrofluorimetric techniques were used. The mesenteric resistance arteries of HD hamsters exhibited (as compared to similar arteries in normals) a decreased contractile response to noradrenaline (1.86+/-0.35 vs. 2.43+/-0.21), and an impeded endothelium dependent relaxation to acetylcholine (approximately 61.40% vs. approximately 79.80%). The association of hyperlipemia with diabetes induced changes in morphology of the resistance arteries consisting in approximately 10% increase of the intima plus media cross-sectional area, approximately 20% decrease of the vascular lumen area, and approximately 2.85 fold augmentation of the wall to lumen ratio. The resistance arteries exhibited structural modifications of the endothelium (up to 8 copies of Weibel-Palade bodies/endothelial cell), and smooth muscle cells (secretory phenotype), and in the vessels media small calcification cores appeared embedded in a hyperplasic extracellular matrix. The vascular mesenteric bed of the HD hamsters contained approximately 2.30 and approximately 1.30 fold increased concentrations of AGE-collagen and pentosidine, respectively, above the normal values. The HD hamsters displayed also modifications that may be dependent on or may lead to an increase in blood pressure, such as: a) approximately 2 fold increase in the activity of serum angiotensin converting enzyme; b) approximately 4.8 fold enhancement of erythrocytes fragility (as a measure of the oxidative stress); c) left ventricular hypertrophy associated with a progressive disarray of cardiomyocyte contractile fibers, interruptions of the Z bands, and accumulation of collagen-rich extracellular matrix indicative of interstitial fibrosis; d) the kidney glomerular capillaries appeared partially or totally collapsed, with a thickened basement membrane which appeared polymorphic, and in some locations made up of successive layers connected by fine bridges and intercalated nodules; in addition, an increase (approximately 1.50 fold) of the mesangial volume was indicative of glomerulosclerosis.
对金黄叙利亚仓鼠进行为期24周的高脂血症（饮食诱导）和糖尿病（链脲佐菌素注射）联合实验模型，其特征为微血管病变和大血管病变普遍存在。我们使用高脂血症 - 糖尿病（HD）仓鼠来研究：a）阻力动脉（平均内径：210 - 250微米）的反应性是否有改变；b）如果有改变，伴随功能改变的结构和生化变化是什么；c）研究高脂血症和糖尿病联合对心肌和肾小球等重要器官所诱导的病理形态学变化。为了实现这些目标，我们使用了血浆成分的生化分析、光镜和电镜、肌动描记法、形态计量学和荧光光谱技术。与正常仓鼠的类似动脉相比，HD仓鼠的肠系膜阻力动脉对去甲肾上腺素的收缩反应降低（1.86±0.35对2.43±0.21），对乙酰胆碱的内皮依赖性舒张受到阻碍（约61.40%对约79.80%）。高脂血症与糖尿病的联合导致阻力动脉形态改变，表现为内膜加中膜横截面积增加约10%，血管腔面积减少约20%，壁腔比增加约2.85倍。阻力动脉表现出内皮结构改变（每个内皮细胞高达8个Weibel - Palade小体）和平滑肌细胞（分泌表型）改变，在血管中膜出现小钙化核心嵌入增生的细胞外基质中。HD仓鼠的肠系膜血管床中AGE - 胶原蛋白和戊糖苷的浓度分别比正常值高出约2.30倍和约1.30倍。HD仓鼠还表现出可能依赖于或可能导致血压升高的改变，例如：a）血清血管紧张素转换酶活性增加约2倍；b）红细胞脆性增强约4.8倍（作为氧化应激的指标）；c）左心室肥厚，伴有心肌细胞收缩纤维逐渐紊乱、Z带中断以及富含胶原蛋白的细胞外基质积聚，提示间质纤维化；d）肾小球毛细血管部分或完全塌陷，基底膜增厚，呈多形性，在某些部位由通过细桥和插入结节连接的连续层组成；此外，系膜体积增加（约1.50倍）提示肾小球硬化。
