【摘要】 目的观察罗格列酮对大鼠胸主动脉损伤后管腔狭窄、基质金属蛋白酶-9(MMP-9)及血浆中肿瘤坏死因子-α(TNF-α)等的影响,探讨罗格列酮减轻血管再狭窄的分子生物学机制。方法用球囊损伤大鼠胸主动脉方法建立损伤模型。雄性SD大鼠随机分成假手术组,罗格列酮组和损伤组。光镜和HE染色观察血管管腔面积和内膜面积变化,原位杂交法检测MMP-9 mRNA表达,免疫组化法检测MMP-9及磷酸化细胞外信号调节激酶1/2(phosphate extracellu lar signal-regu lated k inase1/2,pERK1/2)蛋白表达,放射免疫法检测血浆TNF-α浓度变化。结果罗格列酮可明显减少内膜面积及增加管腔面积(均P<0.05);抑制MMP-9 mRNA和蛋白表达,抑制pERK1/2蛋白表达(均P<0.05);降低血浆中TNF-α浓度(P<0.05)。结论罗格列酮可以显著抑制大鼠主动脉损伤后管腔再狭窄,其机制可能与通过影响信号转导通路pERK1/2而抑制大鼠胸主动脉损伤后MMP-9 mRNA及蛋白表达,同时与降低血浆中TNF-α浓度有关。更多还原

【Abstract】 Objective To investigate the effects of rosiglitazone treatment on vascular restenosis,matrix metalloproteinase-9(MMP-9) and serum tumor necrosis factor-α(TNF-α) after thoracic aorta injury in rats model to explore its molecular biological mechanisms.Methods Rats model were made by thoracic aorta injured by balloon.Ninety male SD rats were randomly divided into sham ligation group,rosiglitazone group and injury group.The areas of lumen of blood vessel and intima were observed by light microscope and HE staining,MMP-9 mRNA expression was detected by hybridization in situ,the protein expressions of MMP-9 and phosphate extracellular signal-regulated kinase1/2(pERK1/2) were determined by immunohistochemistry.Plasma TNF-α level was detected with radioimmunoassay.Results Rosiglitazone significantly decreased intima area,increased lumen area(all P<0.05),inhibited expression of MMP-9 mRNA,protein and pERK1/2 protein(all P<0.05) and reduced plasma TNF-α level(P<0.05).Conclusions Rosiglitazone may attenuate restenosis by suppressing expression of MMP-9 through pERK1/2 signal transduction pathway,and decreasing the release of TNF-α in aorta-injured rats.更多还原