糖尿病大鼠外周血管病变中结缔组织生长因子的表达及其意义

目的 初步探讨结缔组织生长因子在糖尿病外周血管病变发生过程中的作用.方法 24只健康SD大鼠随机分成糖尿病组（A组）和对照组（B组）.A组腹腔注射链脲佐菌素诱导建立糖尿病大鼠模型;12周后处死,取双侧股动脉HE染色观察管壁病变情况,免疫组织化学染色检查CTGF在血管壁中的表达情况,电镜观察血管壁的超微结构.结果 ①HE染色：血管管腔面积与血管外截面面积之比（ST）,A组较B组降低（P＜0.05）血管壁厚度与血管外径之比（WT）,A组较B组增加（P＜0.05）,提示A组管腔狭窄,血管顺应性降低.②免疫组化染色：A组CTGF表达呈阳性（＋）,并主要表达于血管内皮细胞和平滑肌细胞胞浆内;而B组大鼠外周血管CTGF表达基本呈阴性（-）,两组间差异有统计学意义（P＜0.05）.③电镜观察：A组血管内皮细胞及平滑肌细胞肿胀变形,体积增大,胞浆丰富,内有发达的细胞器,以增生的粗面内质网及线粒体为主,血管基底膜增厚.结论STZ诱导的糖尿病大鼠外周血管在病程12周时出现了明显的病理变化,包括动脉管腔狭窄、内皮细胞损伤、平滑肌细胞肥大、细胞外基质增生及血管基底膜增厚;同时,CTGF在内皮细胞及平滑肌细胞上的表达出现显著增强,提示血管病变可能与CTGF表达增加有关.

Expression of connective tissue growth factor in the peripheral vascular lesions of diabetic rat and its significance

Objective To observe the effect of connective tissue growth factor （CTGF） on the development of peripheral vascular lesions of diabetes.Methods Twenty-four Sprague-Dawley rats were divided randomly into Diabetes Mellitus group （A,n =12） and Normal Control group （B,n =12）.Streptozotocin was injected intraperitoneally into the rats in group A to establish the model of diabetic rats.At the 12th week,the rats were sacrificed and their femoral artery were havested.HE stain,immunohistochemistry stain and electron microscope were applied to observe the pathologic structure,the expression of CTGF and ultrastructure of femoral artery,respectively.Results ①HE staining：the ratio of the area of vessel lumen and that of whole vessel in group A was obviously lower than that in group B （P＜0.05）.Accordingly,the ratio of the thickness of vessel wall and the radius of whole vessel in group A was obviously higher than that in group B （P ＜ 0.05）.These results suggested that the vessel lumen in group A became stenotic and the vessel compliance decreased.②Immunohistochemistry staining：In group A,CTGF was expressed in vascular endothelial cells and smooth muscle cells.In group B,the expression of CTGF was almost absent.The difference was much significant （P ＜ 0.01）.③Electron microscope：Swelling,enlargement,deformity and hyperplasia of cytoplasm and endoplasmic reticulum were observed in both endothelial cells and smooth muscle cells.The basement membrane also became thick.Conclusion Evident peripheral vascular lesions were observed in streptozotocin-induced diabetic rats,described as follows：Stenosis of vessel lumen,impairment of vascular endothelial cells,hypertophy of smooth muscle cells,hyperplasia of extra cellular matrix and thickening of basement membrane,at the same time,the expression of CTGF in group A was obviously elevated,which suggested the possible relation between the peripheral vascular lesions and the expression of CTGF.