Yamaji T, Fukuhara T, Kinoshita M
First Department of Internal Medicine, Shiga University of Medical Science, Japan.
Circ Res. 1993 May;72(5):947-57. doi: 10.1161/01.res.72.5.947.
To clarify the mechanism for the well-known increase in microvascular permeability that occurs with diabetes mellitus, we investigated capillary permeability to albumin in diabetic rat myocardium by electron microscopy using albumin-gold (Alb-Au) complexes as a tracer. Diabetes was induced by an intravenous injection of streptozotocin. After 24-32 weeks, hearts from diabetic rats and age-matched control rats were perfused with Krebs-Henseleit bicarbonate buffer containing Alb-Au for 5 or 20 minutes and then fixed and processed for electron microscopy. The binding and transport of Alb-Au by capillary endothelium was quantitatively evaluated. In control rats, Alb-Au particles were found preferentially bound to the luminal plasmalemmal vesicles. In diabetic rats, the labeling of luminal vesicles was more extensive and more pronounced after 5 minutes of perfusion when compared with control vesicles. The plasma membrane proper was also heavily labeled in diabetic rats. After 20 minutes, Alb-Au particles were transported across the capillary endothelium via plasmalemmal vesicles, but they did not penetrate the intercellular junctions in either control or diabetic rats. The vesicular transport of Alb-Au across the capillary endothelium was significantly increased in the diabetic myocardium when compared with control myocardium (percentage of abluminal labeled vesicles, 25.9 +/- 5.5% versus 1.3 +/- 0.5%; p < 0.01). The study on food-restricted rats with body weights close to those of diabetic rats suggested that caloric deficiency alone did not have much effect on capillary permeability. The data indicate that capillary permeability to albumin is markedly increased in diabetic myocardium because of enhanced vesicular transport. This may play an important role in the pathogenesis of diabetic cardiomyopathy.
为阐明糖尿病时微血管通透性增加这一已知现象的机制，我们通过电子显微镜，以白蛋白 - 金（Alb - Au）复合物作为示踪剂，研究了糖尿病大鼠心肌中毛细血管对白蛋白的通透性。通过静脉注射链脲佐菌素诱导糖尿病。24 - 32周后，用含Alb - Au的Krebs - Henseleit碳酸氢盐缓冲液灌注糖尿病大鼠和年龄匹配的对照大鼠的心脏5或20分钟，然后固定并进行电子显微镜处理。定量评估毛细血管内皮对Alb - Au的结合和转运。在对照大鼠中，Alb - Au颗粒优先结合于管腔质膜小泡。在糖尿病大鼠中，与对照小泡相比，灌注5分钟后管腔小泡的标记更广泛且更明显。糖尿病大鼠的质膜本身也有大量标记。20分钟后，Alb - Au颗粒通过质膜小泡穿过毛细血管内皮，但在对照大鼠和糖尿病大鼠中它们均未穿透细胞间连接。与对照心肌相比，糖尿病心肌中Alb - Au穿过毛细血管内皮的小泡转运显著增加（无腔标记小泡的百分比，25.9±5.5%对1.3±0.5%；p<0.01）。对体重接近糖尿病大鼠的食物限制大鼠的研究表明，仅热量不足对毛细血管通透性影响不大。数据表明，由于小泡转运增强，糖尿病心肌中毛细血管对白蛋白的通透性显著增加。这可能在糖尿病性心肌病的发病机制中起重要作用。
