Bhoite-Solomon V, Kessler-Icekson G, Shaklai N
Sackler Institute of Molecular Medicine, Tel-Aviv University Sackler School of Medicine, Israel.
In Vitro Cell Dev Biol Anim. 1993 Aug;29A(8):636-42. doi: 10.1007/BF02634552.
Effects of free hemin on myocardium were investigated using a model of neonatal myocyte primary cultures. Cells were subjected to free hemin at concentrations up to 20 microM and equilibrated for 5 h at 37 degrees C. Distribution of hemin in media, cell sarcolemma, and cell interior was evaluated. Time-dependent reduction in beating rate was monitored throughout the entire concentration range of administrated hemin. With time and in a hemin concentration-dependent manner, arrhythmic beatings which were followed by loss of contractility were observed. In parallel, morphologic changes appeared from granulation to complete loss of cell integrity. At the concentration range studied, hemin also induced a biphasic release of cytosolic enzymes. In the first phase, the fraction of enzyme released was dependent of the ratio of hemin:cells and was correlated with the amount of nonviable cells as monitored by a trypan blue test. In the second phase, the fraction of released enzyme was much larger than that of nonviable cells. The data are interpreted as an indication of complete loss of cytosolic content due to sarcolemma damage in first phase and partial damage to cell interior in the prolonged second phase. It is concluded that in similarity with other amphipathic molecules, free hemin is toxic to the myocardium.
使用新生心肌细胞原代培养模型研究了游离血红素对心肌的影响。使细胞暴露于浓度高达20微摩尔的游离血红素中，并在37℃下平衡5小时。评估了血红素在培养基、细胞膜和细胞内的分布。在整个血红素给药浓度范围内监测心率随时间的降低情况。随着时间的推移以及血红素浓度的增加，观察到心律失常，随后出现收缩力丧失。同时，形态学变化从颗粒化到细胞完整性完全丧失。在所研究的浓度范围内，血红素还诱导了胞质酶的双相释放。在第一阶段，释放的酶分数取决于血红素与细胞的比例，并与通过台盼蓝试验监测的非存活细胞数量相关。在第二阶段，释放的酶分数远大于非存活细胞的分数。这些数据被解释为第一阶段由于细胞膜损伤导致胞质内容物完全丧失，以及在延长的第二阶段细胞内部部分受损的迹象。结论是，与其他两亲性分子类似，游离血红素对心肌有毒性。
