摘要
目的用腹腔注射链脲佐菌素(STZ)的方法制备大鼠糖尿病模型,通过检测糖尿病大鼠主动脉中纤溶酶原激活物抑制物-1(PAI-1)及基质金属蛋白酶-9(MMP-9)的表达和血浆中PAI-1及内皮素(ET)含量的改变,观察羟苯磺酸钙对糖尿病大鼠主动脉的保护作用并探讨其机制。方法用STZ建立大鼠糖尿病(DM)模型,将DM模型大鼠随机分为羟苯磺酸钙组和糖尿病组,并设正常对照组,每组10只。羟苯磺酸钙组每天给予羟苯磺酸钙0.15mg/g灌胃,其余两组给予相同剂量的蒸馏水。各组大鼠分别干预8周。处死前抽血备测血清学指标,处死后固定主动脉留做形态学观察。分别用放射免疫法和酶联免疫吸附法(ELISA)测定血浆中ET和PAI-1含量。用免疫组化技术检测大鼠主动脉PAI-1、MMP-9的表达,光镜、电镜下观察主动脉病理形态的改变。结果与糖尿病组相比,羟苯磺酸钙能降低血浆ET和PAI-1的含量(P<0.05),改善大鼠主动脉病理损伤,减少主动脉局部PAI-1和MMP-9的表达(P<0.05)。糖尿病组大鼠主动脉内膜增厚,内皮细胞肿胀,平滑肌细胞增生、排列紊乱。羟苯磺酸钙组大鼠主动脉上述病变明显减轻。结论羟苯磺酸钙能显著降低糖尿病大鼠ET、PAI-1和MMP-9的表达量,抑制血小板聚集,降低血管通透性,保护血管内皮,延缓动脉硬化,稳定粥样斑块。
Objective To investigate the effect of calcium dobesilate on the aorta of diabetic rats and explore its possible mechanism.Methods The Diabetes mellitus（DM） model was established by a single injection of streptozotocin（STZ）and DM rats were randomly divided into the calcium dobsilate group and the diabetic group.Normal rats served as the normal group.Each group contained 10 rats.In the calcium dobsilate group,rats were treated intragastrically with 0.15 mg/g calcium dobsilate every day while the same dose of distilled-water was applied in the other groups.The treatment lasted for 8 weeks.Before being sacrificed,blood samples were drawn to measure serum indicators.After being sacrificed,the aorta was fixed to observe morphological changes.Plasma endothelin（ET） and Plasminogen activator inhibitor-1（PAI-1） levels were measured respectively with radioimmunoassay and enzyme linked immunosorbent assay（ELISA）.Expression of PAI-1 and matrix metalloprotein-9（MMP-9）in the aorta were determined with immunohistological chemistry.Results Compared with the diabetic group,the plasma level of ET and PAI-1 were decreased（P 0.05） by calcium dobesilate.Expression of PAI-1 and MMP-9 in the aorta was decreased by calcium dobesilate.Rats in the DM group showed abnormal aortic ultra-structure,including incrassated intima,varicose endothelial cells,proliferation and disorder of smooth muscle cells.These phenomena were significantly alleviated in the calcium dobesilate group.Conclusion Calcium dobesite can protect blood vessel endothelium,inhibit platelet aggregation,delay arteriosclerosis,stabilize atheromatous plaque via down-regulation of ET and PAI-1 in plasma and inhibition of PAI-1 and MMP-9 expression in the aorta.
出处
《山东大学学报（医学版）》
CAS
北大核心
2010年第10期4-8,13,共6页
Journal of Shandong University:Health Sciences
