目的检测ADAMTS-(a disintegrin and metalloprotease with throm- spondin type 1 motifs)在急、慢性柯萨奇病毒B3(CVB3)心肌炎小鼠心肌组织中的表达,并分析其与心肌纤维化的关系。方法以CVB3单次感染或重复增量感染Ba1b／C小鼠分别建...目的检测ADAMTS-(a disintegrin and metalloprotease with throm- spondin type 1 motifs)在急、慢性柯萨奇病毒B3(CVB3)心肌炎小鼠心肌组织中的表达,并分析其与心肌纤维化的关系。方法以CVB3单次感染或重复增量感染Ba1b／C小鼠分别建立急性病毒性心肌炎(急性组,20只)及慢性病毒性心肌炎(慢性组,25只)模型,同期小鼠腹腔无菌注射等剂量不含病毒的EMEM液作为各自正常对照组(均为10只)。以苦味酸天狼猩红行心肌胶原组织特异性染色,并运用图像分析软件计算心肌组织中的胶原容积积分(collagen volume fraction,CVF,％;用反转录-聚合酶链反应(RT-PCR)和免疫组织化学方法分别检测小鼠心肌组织中ADAMTS-1基因水平和蛋白水平的表达。结果两组病毒性心肌炎小鼠心肌组织中CVF显著增加,且慢性组更为显著(P<0．01):急、慢性组ADAMTS-1 mRNA均明显高于其正常对照组,尤以慢性组升高更为显著(P<0．05);免疫组织化学检测结果显示, ADAMTS-1在心肌组织细胞胞质内表达;各实验组小鼠心肌组织中ADAMTS-1 mRNA的表达与CVF呈正相关。结论ADAMTS-1在急、慢性病毒性心肌炎心肌组织中呈进行性增加并与胶原增生密切相关,表明ADAMTS-1可能通过调节胶原代谢参与心肌纤维化的发生、发展。展开更多
Insufficient growth and rarefaction of capillaries, followed by endothelial dysfunction may represent one of the most critical mechanisms involved in heart damage. In this study we examined histochemical and ultrastru...Insufficient growth and rarefaction of capillaries, followed by endothelial dysfunction may represent one of the most critical mechanisms involved in heart damage. In this study we examined histochemical and ultrastructural changes in myocardial capillary endothelium in two models of heart failure streptozotocin-induced diabetes mellitus （STZ） and NO-deficient hypertension in male Wistar rats. Diabetes was induced by a single i.v. dose of STZ （45 mg/kg） and chronic 9-week stage was analysed. To induce NO-deficient hypertension, animals were treated with inhibitor of NO synthase Lnitroarginine methylester （L-NAME） （40 mg/kg） for 4 weeks. Left ventricular tissue was processed for enzyme catalytic histochemistry of capillary alkaline phosphatase （A1Ph）, dipeptidyl peptidase IV （DPP IV）, and endothelial NO synthase/NADPH-diaphorase （NOS） and for ultrastructural analysis. In diabetic and hypertensive rats, lower/absent A1Ph and DPP IV activities were found in focal micro-areas. NOS activity was significantly reduced and persisted only locally. Quantitative evaluation demonstrated reduction of reaction product intensity of A1Ph, DPP and NOS by 49.50%,74.36%, 20.05% in diabetic and 62.93%, 82.71%, 37.65% in hypertensive rats. Subcellular alterations of endothelial cells were found in heart of both groups suggesting injury of capillary function as well as compensatory processes. Endothelial injury was more significant in diabetic animals, in contrast the adaptation was more evident in hypertensive ones. Concluding： both STZ-induced diabetes- and NO-deficient hypertension-related cardiomyopathy were accompanied by similar features of structural remodelling of cardiac capillary network manifested as angiogenesis and angiopathy. The latter was however, predominant and may accelerate disappearance of capillary endothelium contributing to myocardial dysfunction.展开更多
文摘目的检测ADAMTS-(a disintegrin and metalloprotease with throm- spondin type 1 motifs)在急、慢性柯萨奇病毒B3(CVB3)心肌炎小鼠心肌组织中的表达,并分析其与心肌纤维化的关系。方法以CVB3单次感染或重复增量感染Ba1b／C小鼠分别建立急性病毒性心肌炎(急性组,20只)及慢性病毒性心肌炎(慢性组,25只)模型,同期小鼠腹腔无菌注射等剂量不含病毒的EMEM液作为各自正常对照组(均为10只)。以苦味酸天狼猩红行心肌胶原组织特异性染色,并运用图像分析软件计算心肌组织中的胶原容积积分(collagen volume fraction,CVF,％;用反转录-聚合酶链反应(RT-PCR)和免疫组织化学方法分别检测小鼠心肌组织中ADAMTS-1基因水平和蛋白水平的表达。结果两组病毒性心肌炎小鼠心肌组织中CVF显著增加,且慢性组更为显著(P<0．01):急、慢性组ADAMTS-1 mRNA均明显高于其正常对照组,尤以慢性组升高更为显著(P<0．05);免疫组织化学检测结果显示, ADAMTS-1在心肌组织细胞胞质内表达;各实验组小鼠心肌组织中ADAMTS-1 mRNA的表达与CVF呈正相关。结论ADAMTS-1在急、慢性病毒性心肌炎心肌组织中呈进行性增加并与胶原增生密切相关,表明ADAMTS-1可能通过调节胶原代谢参与心肌纤维化的发生、发展。
文摘Insufficient growth and rarefaction of capillaries, followed by endothelial dysfunction may represent one of the most critical mechanisms involved in heart damage. In this study we examined histochemical and ultrastructural changes in myocardial capillary endothelium in two models of heart failure streptozotocin-induced diabetes mellitus （STZ） and NO-deficient hypertension in male Wistar rats. Diabetes was induced by a single i.v. dose of STZ （45 mg/kg） and chronic 9-week stage was analysed. To induce NO-deficient hypertension, animals were treated with inhibitor of NO synthase Lnitroarginine methylester （L-NAME） （40 mg/kg） for 4 weeks. Left ventricular tissue was processed for enzyme catalytic histochemistry of capillary alkaline phosphatase （A1Ph）, dipeptidyl peptidase IV （DPP IV）, and endothelial NO synthase/NADPH-diaphorase （NOS） and for ultrastructural analysis. In diabetic and hypertensive rats, lower/absent A1Ph and DPP IV activities were found in focal micro-areas. NOS activity was significantly reduced and persisted only locally. Quantitative evaluation demonstrated reduction of reaction product intensity of A1Ph, DPP and NOS by 49.50%,74.36%, 20.05% in diabetic and 62.93%, 82.71%, 37.65% in hypertensive rats. Subcellular alterations of endothelial cells were found in heart of both groups suggesting injury of capillary function as well as compensatory processes. Endothelial injury was more significant in diabetic animals, in contrast the adaptation was more evident in hypertensive ones. Concluding： both STZ-induced diabetes- and NO-deficient hypertension-related cardiomyopathy were accompanied by similar features of structural remodelling of cardiac capillary network manifested as angiogenesis and angiopathy. The latter was however, predominant and may accelerate disappearance of capillary endothelium contributing to myocardial dysfunction.
