OLETF糖尿病大鼠心肌光镜与透射电镜病理改变的观察

A light and electron microscopic observation of myocardial structural changes in OLETF diabetic rats

目的使用光镜与透射电镜,观察OLETF糖尿病大鼠在糖尿病病程中晚期的心肌病理改变。方法以7只OLETF糖尿病大鼠作为实验动物模型,做OGTT试验诊断并了解糖尿病病程。另以7只LETO大鼠为对照。鼠龄58周时检测血浆血脂、胰岛素、C-肽水平,评估胰岛功能及脂代谢状况。股动脉插管测量血压、颈动脉逆行插管入左心室测量左室内压以评估心功能。石蜡切片HE、PAS、VG染色观察心肌光镜组织结构。两组各取3只大鼠超薄切片透射电镜观察心肌超微结构,测量心肌壁毛细血管基膜厚度并进行比较。结果OG-TT试验显示34周后80%OLETF糖尿病大鼠已发生糖尿病,鼠龄58周时三酰甘油、胆固醇较对照组明显增加(P<0.05)。左心室压下降速率(-dp/dt)低于对照组(P<0.05)。OLETF糖尿病大鼠HE染色显示心肌细胞肥大,肌纤维收缩呈波浪状;PAS,VG染色显示心肌间质胶原纤维增多。超薄切片透射电镜观察显示心肌细胞挛缩、肌原纤维收缩带形成,心肌间质胶原沉积,毛细血管基膜增厚。OLETF糖尿病大鼠的基膜厚度为(64.33±4.38)nm,较LETO对照组大鼠(46.09±3.62)nm明显增厚(P<0.001)。结论58周龄OLETF糖尿病大鼠的心肌病理改变为心肌细胞挛缩、心肌间质胶原沉积和毛细血管基膜增厚,并与左心室舒张功能减退同时存在。

Objective To observe pathologic changes of myocardium in Otsuka Long-Evans Tokushima Fatty （OLETF） diabetic rats using light and electron microscope. Methods Seven OLETF diabetic rats were used as animal models and diabetic stage was determined by oral glucose tolerance test. Seven LETO rats were taken as control group. When the rats were 58 weeks old, serum lipoproteins, insulin,C-peptide were tested by kit. Blood pressure,left ventricular pressure were determined separately by femoral artery and carotid artery catheterization. The myocardial tissues stained with HE, PAS, VG were observed by light microscope. The myocardial ultrastructure was observed with electron microscope and capillary basement membrane thickness was measured in 3 rats from both groups. Results Compared with normal control group, levels of TG,CHO in OLETF diabetic rats were higher （P〈0.05）, the maximal rate of the left ventricular pressure fall （peak negative dp/dt） was lower （P 〈0.05）. HE staining showed cardiomyocyte hypertrophy and contraction; PAS staining showed excessive accumulation of glycogen and VG staining showed an accumulation of extracellular collagen.Transmission electron microscope showed cardiomyocyte contraction, formation of myofibril contraction bands, accumulation of extracellular matrix, thickening of capillary basement membrane. The basement membrane thickness in diabetes group （ 64.33 ± 4.38 ） nm was thicker than that of the control group （46.09 ±3.62） nm （P〈0. 001）. Conclusions The pathologic changes of myocardium are cardiomyocye contraction,myocardial interstitial fibrosis and thickening of basement membrane, coexisting with left ventricular diastolic dysfunction.