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目的:研究基质金属蛋白酶-9(MMP-9)与动脉粥样硬化(AS)斑块内血管生成的关系及强力霉素干预的效果。方法:将36只雄性Wistar大鼠随机分为对照组(A组,普通饮食喂养)、AS组(B组)和强力霉素干预组(C组),B组和C组均给予高脂饮食+维生素D3腹腔注射,C组同时给予强力霉素腹腔注射。采用酶法并以全自动生化分析仪测量血脂,双抗体夹心ABC-ELISA法检测血清MMP-9的水平。取主动脉切片行HE染色,观察斑块形态,计数易损斑块的数目。对内皮细胞标记物CD34行免疫组织化学染色法以检测斑块内新生血管密度。结果:B组和C组各项血脂的水平无明显差异,但均明显高于A组(P<0.05)。B组和C组血清MMP-9的水平明显高于A组(P<0.05),B组又高于C组(P<0.05)。与B组比较,C组易损斑块数、CD34+面积/扫描面积(R)比均降低(P<0.01)。结论:强力霉素能增强斑块稳定性,这种作用可能是通过降低MMP-9的水平进而减少了斑块内血管生成。
Objective: To investigate the relationship between matrix metalloproteinase-9 (MMP-9) and angiogenesis in atherosclerotic plaque and the effect of doxycycline intervention. Methods: Thirty-six male Wistar rats were randomly divided into control group (group A, normal diet group), AS group (group B) and doxycycline intervention group (group C). Groups B and C were given high fat diet + Vitamin D3 intraperitoneal injection, while C group given doxycycline intraperitoneal injection. Serum lipids were measured by enzymatic method and automatic biochemical analyzer. Serum MMP-9 levels were detected by double antibody sandwich ABC-ELISA. Aortic sections were taken HE staining, plaque morphology, count the number of vulnerable plaque. The endothelial cell marker CD34 was subjected to immunohistochemical staining to detect plaque neovascular density. Results: There was no significant difference in the levels of blood lipids in group B and group C, but both were significantly higher than those in group A (P <0.05). The levels of serum MMP-9 in group B and group C were significantly higher than those in group A (P <0.05), and those in group B were significantly higher than those in group C (P <0.05). Compared with group B, the numbers of vulnerable plaque, CD34 + area / scan area (R) in group C were all decreased (P <0.01). CONCLUSION: Doxycycline enhances plaque stability, possibly by reducing plaque angiogenesis by decreasing MMP-9 levels.