Ishiura S, Nonaka I, Sugita H
J Cell Sci. 1986 Jul;83:197-212. doi: 10.1242/jcs.83.1.197.
A single injection of a local anaesthetic, bupivacaine, into the soleus muscle of adult rat has a severe mytoxic effect, i.e. rapid dissolution of myofilaments and degradation of myofibrillar proteins shortly after injection. Increased lysosomal enzymes were observed in homogenates of affected muscle. The activity of potent proteolytic enzyme, cathepsins B and L (assayed against a new synthetic substrate succinyl-Tyr-Met-naphthylamide), gradually increased and reached a plateau value that was 11-fold greater than the control 48 h after bupivacaine injection. The chronological change in the activity of cathepsins B and L was reflected in the myofibrillar protein pattern in bupivacaine-treated muscle. To determine whether the increase in lysosomal peptide hydrolases is due to activation of muscle lysosomes or not, mononuclear cells were separated from both injected and control muscles. The activity of cathepsins B and L in the lysate from injured muscle was 180-fold higher than the control. Affinity-purified antibody was used to study the intracellular localization of cathepsin B by immunohistochemical procedures. The results were consistent with the biochemical observation that the main source of cathepsin B in muscle homogenates was infiltrated mononuclear cells. Therefore, we conclude that the increased lysosomal enzymes may be derived mainly from mononuclear cells (macrophages), not from muscle lysosomes, in bupivacaine-induced acute muscle degeneration.
向成年大鼠比目鱼肌单次注射局部麻醉药布比卡因具有严重的肌毒性作用，即注射后不久肌丝迅速溶解，肌原纤维蛋白降解。在受影响肌肉的匀浆中观察到溶酶体酶增加。强效蛋白水解酶组织蛋白酶B和L的活性（以新的合成底物琥珀酰 - 酪氨酰 - 甲硫氨酰 - 萘酰胺测定）逐渐增加，并在布比卡因注射后48小时达到比对照高11倍的平台值。组织蛋白酶B和L活性的时间变化反映在布比卡因处理肌肉的肌原纤维蛋白模式中。为了确定溶酶体肽水解酶的增加是否由于肌肉溶酶体的激活，从注射和对照肌肉中分离出单核细胞。受伤肌肉裂解物中组织蛋白酶B和L的活性比对照高180倍。使用亲和纯化抗体通过免疫组织化学方法研究组织蛋白酶B的细胞内定位。结果与生化观察一致，即肌肉匀浆中组织蛋白酶B的主要来源是浸润的单核细胞。因此，我们得出结论，在布比卡因诱导的急性肌肉变性中，溶酶体酶增加可能主要源自单核细胞（巨噬细胞），而非肌肉溶酶体。
