Gutiérrez J M, Arce V, Brenes F, Chaves F
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José.
Exp Mol Pathol. 1990 Feb;52(1):25-36. doi: 10.1016/0014-4800(90)90055-i.
The effects of a myotoxic phospholipase A2 isolated from the venom of the crotaline snake Bothrops asper on skeletal muscle myofibrils were studied by histological, ultrastructural, immunohistochemical, and biochemical parameters. Myotoxin induced a rapid and prominent muscle necrosis after intramuscular injection in mice. In this process, myofibrils were affected and three main changes were observed: (A) Initially, they were hypercontracted, eventually forming "clumped," dense masses which alternated with spaces devoid of myofilaments in the cytoplasm. This initial stage is probably due to hypercontraction resulting from a calcium influx after toxin-induced sarcolemmal damage. (B) A second change occurred between 3 and 6 hr, when the clumped or hypercontracted pattern changed to a "hyaline" pattern in which myofilaments were relaxed and had a more uniform distribution in the cellular space. Although there was not a widespread degradation of myofibrillar components at this stage, desmin started to be lost in samples obtained as early as 15 min after toxin injection, and alpha-actinin was almost absent by 7 hr. Thus, it is proposed that this shift may be due to a selective proteolytic degradation of structurally relevant components, particularly alpha-actinin. As a consequence, the mechanical integration of myofilaments is impaired, precluding hypercontraction. (C) Finally, at later time periods (24, 48, and 72 hr), there was widespread degradation of myofibrillar proteins, probably caused by proteases derived from inflammatory cells such as neutrophils and macrophages, whose numbers in necrotic muscle increased markedly at these time periods.
通过组织学、超微结构、免疫组织化学和生化参数研究了从蝰蛇科蛇类矛头蝮毒液中分离出的一种肌毒性磷脂酶A2对骨骼肌肌原纤维的影响。肌毒素在小鼠肌肉内注射后可诱导快速且显著的肌肉坏死。在此过程中，肌原纤维受到影响，观察到三个主要变化：（A）最初，它们过度收缩，最终形成“团块”状致密物质，与细胞质中无肌丝的区域交替出现。这个初始阶段可能是由于毒素诱导肌膜损伤后钙内流导致的过度收缩。（B）第二个变化发生在3至6小时之间，此时团块状或过度收缩模式转变为“透明”模式，其中肌丝松弛并在细胞空间中分布更均匀。尽管在此阶段肌原纤维成分没有广泛降解，但早在毒素注射后15分钟获得的样本中结蛋白就开始丢失，到7小时时α-辅肌动蛋白几乎消失。因此，有人提出这种转变可能是由于结构相关成分，特别是α-辅肌动蛋白的选择性蛋白水解降解。结果，肌丝的机械整合受损，无法进行过度收缩。（C）最后，在后期（24、48和72小时），肌原纤维蛋白广泛降解，可能是由中性粒细胞和巨噬细胞等炎症细胞衍生的蛋白酶引起的，在这些时间段坏死肌肉中这些细胞的数量显著增加。
