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目的:维甲酸是维生素A的体内衍生物,通过受体介导的基因,包括基质金属蛋白酶基因表达改变,发挥多种生物学效能。维甲酸细胞内转运和代谢由细胞视黄醇结合蛋白-1(CRBP-1)调节。在组织修复过程中肉芽组织表达CRBP-1。为探讨心肌梗死后心室重构的机制,检测了大鼠心肌梗死模型中CRBP-1的表达。方法:通过结扎左冠状动脉前降支获得大鼠心肌梗死模型。80只成年雄性Wistar大鼠分为3组。假手术组10只大鼠,假手术后6天处死取心脏。心肌梗死组50只大鼠,每时间点10只,分别于术后3天、6天、15天、30天和45天处死大鼠取心脏。蛋白检测组20只心肌梗死大鼠,每时间点5只,分别于术后3天、6天、15天和45天处死大鼠取心脏标本用于蛋白检测。心脏从心尖至心底部分为四部分,经过固定和石蜡包埋做成切片。苏木素—伊红、Masson’s trichrome染色以及兔抗CRBP-1抗体和鼠抗α平滑肌(α-SM)肌动蛋白抗体经免疫组织化学染色。并应用Western印迹法检测CRBP-1和α-SM肌动蛋白。结果:心肌梗死组大鼠均获得了大面积心肌梗死,按左心室周长法计算,梗死面积从43.3%到58.1%[平均(48.8±3.6)%]。心肌梗死组各时间点心肌梗死面积差异均无显著性。心肌梗死组各时间点大鼠右心室重量和右心室重量/体重以及左心室横径长度和长度/体重均较假手术组显著增加(P均<0.05),提示心肌梗死后左心室重构明显。观察见病区心肌细胞坏死、胶原沉积以及左心室重构。免疫组织化学染色显示,术后3天和6天心肌梗死心内、心外膜区域均有纤维母细胞浸润和心肌细胞坏死以及CRBP-1表达。术后6天和术后15天,心肌梗死区域α-SM肌动蛋白阳性的肌纤维母细胞有CRBP-1表达,这种表达于术后30天逐渐减低。结论:大鼠心肌梗死模型中纤维母细胞短暂而迅速地表达CRBP-1,提示CRBP-1和维甲酸可能在心肌梗死后心室重构中起重要作用。
AIM: Retinoic acid is an in vivo derivative of vitamin A that exerts multiple biological effects through receptor-mediated gene expression, including changes in the expression of matrix metalloproteinases. Retinoic acid intracellular transport and metabolism is regulated by the cellular retinol binding protein-1 (CRBP-1). Granulation tissue expressed CRBP-1 during tissue repair. To investigate the mechanism of ventricular remodeling after myocardial infarction, the expression of CRBP-1 in rat myocardial infarction model was detected. Methods: Myocardial infarction model was obtained by ligating left anterior descending coronary artery. Eighty adult male Wistar rats were divided into three groups. Sham operation group 10 rats, 6 days after sham operation sacrifice the heart. 50 rats in myocardial infarction group, 10 rats in each time point, were sacrificed at 3, 6, 15, 30 and 45 days after operation. In the protein test group, 20 rats with myocardial infarction were sacrificed at 5 time points and the rats were sacrificed at 3 days, 6 days, 15 days and 45 days after operation respectively for protein detection. Heart from the apex to the heart of the four parts, after fixed and paraffin embedded into slices. Hematoxylin-Eosin, Masson’s trichrome staining and rabbit anti-CRBP-1 antibody and mouse anti-α smooth muscle (α-SM) actin antibody were stained immunohistochemically. Western blotting was used to detect CRBP-1 and α-SM actin. RESULTS: Large myocardial infarction was achieved in all myocardial infarction rats. The infarct size ranged from 43.3% to 58.1% [mean (48.8 ± 3.6)%] according to the left ventricular perimeter method. Myocardial infarction group myocardial infarct size at any time point was no significant difference. Right ventricular weight and right ventricular weight / body weight and left ventricular transverse length and length / body weight of rats in myocardial infarction group were significantly higher than those in sham operation group at each time point (all P <0.05), suggesting that left ventricular remodeling was obvious after myocardial infarction . Myocardial cell necrosis, collagen deposition, and left ventricular remodeling were observed in the ward. Immunohistochemical staining showed fibroblast infiltration and cardiomyocyte necrosis as well as CRBP-1 expression in myocardial and epicardial areas at 3 days and 6 days after operation. Six days after operation and 15 days after operation, α-SM actin-positive myofibroblasts in the infarcted area had CRBP-1 expression, which gradually decreased 30 days after the operation. CONCLUSION: The transient and rapid expression of CRBP-1 by fibroblasts in a rat myocardial infarction model suggests that CRBP-1 and retinoic acid may play an important role in ventricular remodeling after myocardial infarction.