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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 establish diabetic rat model by intraperitoneal injection of streptozotocin (STZ), and to detect the expression of plasminogen activator inhibitor-1 (PAI-1) and matrix metalloproteinase-9 (MMP-9) and the content of plasma PAI-1 and endothelin (ET). To observe the protective effect of calcium dobesilate on the aorta in diabetic rats and its mechanism. Methods The rat model of diabetes mellitus (DM) was established by STZ. The DM model rats were randomly divided into calcium dobesilate group and diabetic group, and the normal control group, 10 rats in each group. The calcium dobesilate group was orally administered 0.15 mg / g calcium dobesilate per day, and the remaining two groups were given the same dose of distilled water. Each group of rats were intervened for 8 weeks. Blood samples were taken before sacrifice for serological tests, and the aorta was fixed after sacrifice for morphological observation. Plasma ET and PAI-1 levels were determined by radioimmunoassay and enzyme-linked immunosorbent assay (ELISA). The expression of PAI-1 and MMP-9 in the aorta of rats was detected by immunohistochemistry. The pathological changes of the aorta were observed under light and electron microscope. Results Compared with diabetic group, calcium dobesilate could decrease the levels of plasma ET and PAI-1 (P <0.05), ameliorate the pathological changes of the aorta and decrease the expressions of PAI-1 and MMP-9 in the aorta ( P <0.05). Diabetic rats aortic intima thickening, endothelial cell swelling, smooth muscle cell proliferation, arranged disorder. The above lesions in the aorta of calcium dobesilate rats were significantly reduced. Conclusion Calcium dobesilate can significantly reduce the expression of ET, PAI-1 and MMP-9 in diabetic rats, inhibit platelet aggregation, decrease vascular permeability, protect vascular endothelium, delay arteriosclerosis and stabilize atherosclerotic plaque.