Granchelli J A, Hudecki M S, Pollina C M
Department of Biological Sciences, SUNY at Buffalo 14260.
Res Commun Chem Pathol Pharmacol. 1994 Jun;84(3):351-62.
Species-specific differences in the inflammatory response, specifically with regard to mast cells, have been proposed to explain the phenotypic variation among dystrophin-deficient humans, and mdx mice (Gorospe et al., 1994). To test this hypothesis we have intramuscularly injected a mast cell secretogogue into both dystrophin-negative mdx and dystrophin-positive normal mice. Mast cell activity was determined by measuring the activity of mast cell tryptase, while creatine kinase activity was used to determine the course of muscle damage in vivo. Area of damage around the injection site was measured at autopsy, and used as an indication of relative sensitivity to the secretogogue effect of compound 48/80. Mdx mice exhibited more damage in response to intramuscular injection than normal control mice. In addition, mdx mice showed a substantial increase in plasma tryptase activity, followed by a large increase in muscle creatine kinase activity. On the other hand, dystrophin-positive normal controls injected with 48/80 liberated little CK or tryptase activity. These results are consistent with the hypothesis that species-specific differences in mast cell activity, or sensitivity to mast cell products could account for the variation in pathology seen in dystrophin-deficient animals.
有人提出，炎症反应中的物种特异性差异，特别是与肥大细胞有关的差异，可以解释肌营养不良蛋白缺乏的人类和mdx小鼠之间的表型差异（Gorospe等人，1994年）。为了验证这一假设，我们将肥大细胞促分泌剂肌肉注射到肌营养不良蛋白阴性的mdx小鼠和肌营养不良蛋白阳性的正常小鼠体内。通过测量肥大细胞类胰蛋白酶的活性来确定肥大细胞的活性，同时使用肌酸激酶活性来确定体内肌肉损伤的进程。在尸检时测量注射部位周围的损伤面积，并将其用作对化合物48/80促分泌剂作用相对敏感性的指标。与正常对照小鼠相比，mdx小鼠在肌肉注射后表现出更多的损伤。此外，mdx小鼠血浆类胰蛋白酶活性大幅增加，随后肌肉肌酸激酶活性大幅增加。另一方面，注射了48/80的肌营养不良蛋白阳性正常对照释放的肌酸激酶或类胰蛋白酶活性很少。这些结果与以下假设一致，即肥大细胞活性或对肥大细胞产物的敏感性的物种特异性差异可能是肌营养不良蛋白缺乏动物病理变化差异的原因。
