高血压合并糖尿病大鼠心肌毛细血管内皮细胞超微结构及eNOS的变化

目的:探讨高血压合并糖尿病(DM)对心肌毛细血管内皮细胞超微结构及内皮型一氧化氮合酶(eNOS)表达的影响。方法:自发性高血压大鼠(SHR)及SD大鼠腹腔注射链脲佐菌素(STZ)结合高能量饲料诱导DM模型。分为4组:正常SD大鼠组(SD组)、SHR组、单纯DM组(DM组)与自发性高血压合并DM大鼠组(SHDM组)。电镜观察各组心肌毛细血管内皮细胞超微结构,免疫组化法测定各组eNOS在毛细血管内皮细胞的表达。结果:SHR、DM和SHDM组心肌毛细血管超微结构明显改变,包括内皮细胞水肿,细胞膜向管腔内呈指状突起,管腔狭窄、不规则等,这些现象在DM组与SHDM组更明显。与SD组比较,SHR组基底膜稍有增厚,但无显著性差异(31.31±4.19nmvs28.64±3.62nm,P>0.05),而DM组(46.58±5.32nm)和SHDM(51.50±4.62nm)组基底膜显著增厚(与SD及SHR组比较,均P<0.01)。SHDM组心肌组织eNOS表达显著低于SHR组及DM组。结论:高血压与DM共存时对心肌毛细血管内皮细胞超微结构及功能有协同损害作用。

Ultrastructural Changes and Expression of eNOS in Myocardial Capillary Endothelial Cells in Rats with Hypertension and Diabetes Mellitus

Objective:To investigate ultrastructural changes and expression of eNOS in rat myocardial capillary endothelial cells as a response to hypertension with diabetes mellitus.Method:The rat model of hypertension with diabetes mellitus(SHDM) and the rat model of diabetes mellitus(DM) alone were induced by an intraperitoneal injection of streptozotocin combined with high fat diet in SD rats and spontaneously hypertensive rats(SHR),respectively.The groups were as follows:SD,DM,SHR,and SHDM.Ultrastructure of the myocardial capillaries was examined by transmission electron microscopy and the expression of endothelial nitric oxide synthase(eNOS) was detected by immunohistochemistry.Results:Ultrastructural alterations of myocardial capillaries in SHR,DM and SHDM were edematous endothelial cell,endothelial protrusions into lumen and narrowed /or irregular lumen respectively.These alterations indicated that cell injury was more significant in the myocardium of DM and SHDM.Thickening of basal lamina in myocardial capillaries with SHR was less considerable compared with SD(31.31±4.19nm vs.28.64±3.62nm,P>0.05),while thickening was a prominent feature of DM(46.58±5.32) nm and SHDM(51.50±4.62) nm(compared with SD or SHR,P<0.01).The expression of eNOS in myocardial tissue was significantly lower in SHDM than in SHR or DM.Conclusion:These results suggest that a combination of hypertension and diabetes mellitus enhanced the damage of myocardial capillaries endothelial cell ultrastructure and function more than either hypertension or diabetes mellitus alone.