St Pierre B A, Tidball J G
School of Nursing, Department of Physiological Science, University of California, Los Angeles 90024-1527.
J Appl Physiol (1985). 1994 Jul;77(1):290-7. doi: 10.1152/jappl.1994.77.1.290.
The hypothesis that distinct populations of macrophages are associated with muscle necrosis and regeneration was examined in Wistar rat soleus muscle after 10 days of hindlimb suspension and 2, 4, and 7 days after the resumption of weight bearing. Necrosis was identified using histological features, such as muscle fiber infiltration, and regeneration was identified using immunohistochemical techniques for developmental myosin heavy chain (dMHC). Light-microscopic observations show that necrotic fibers in 2-day reloaded soleus muscle were invaded by ED1+ and Ia+ macrophages. The number of invaded fibers in muscles reloaded for 2 days increased to 2.8/mm2 compared with 0.2/mm2 in age-matched normal muscle but returned to control values by the 4th day of resumed weight bearing. In the interstitial spaces of 2-day recovery muscle, ED1+ and Ia+ macrophages numbered 369 and 332/mm2, respectively, compared with 12 and 72/mm2, respectively, in control soleus. After 7 days of reloading, the number of ED1+ cells was similar to that of control. Ia+ macrophages decreased to 240/mm2 at 4 days but after 7 days rose above control values to 429/mm2. ED2+ macrophages in 4- and 7-day reloaded soleus increased 70-80% in the interstitial spaces compared with control but were not observed to infiltrate necrotic muscle fibers at any time points. Immunohistochemistry and immunoblots using a monoclonal anti-dMHC antibody demonstrate a greater proportion of myofibers expressing dMHC isoforms after 4 and 7 days of reloading. These findings indicate that macrophage subpopulations are associated with distinct stages during the recovery process from hindlimb suspension: ED1+ macrophages are associated with muscle necrosis, whereas ED2+ cells are associated with muscle regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)
在对Wistar大鼠比目鱼肌进行10天的后肢悬吊以及恢复负重2天、4天和7天后，研究了不同巨噬细胞群体与肌肉坏死和再生相关的假说。利用组织学特征（如肌纤维浸润）鉴定坏死情况，利用发育性肌球蛋白重链（dMHC）免疫组化技术鉴定再生情况。光学显微镜观察显示，在恢复负重2天的比目鱼肌中，ED1+和Ia+巨噬细胞侵入坏死纤维。与年龄匹配的正常肌肉中每平方毫米0.2根相比，恢复负重2天的肌肉中被侵入的纤维数量增加到每平方毫米2.8根，但在恢复负重第4天时恢复到对照值。在恢复负重2天的肌肉间质中，ED1+和Ia+巨噬细胞分别为每平方毫米369个和332个，而对照比目鱼肌中分别为每平方毫米12个和72个。恢复负重7天后，ED1+细胞数量与对照相似。Ia+巨噬细胞在第4天时降至每平方毫米240个，但在7天后升至高于对照值，达到每平方毫米429个。与对照相比，恢复负重4天和7天的比目鱼肌中ED2+巨噬细胞在间质中增加了70 - 80%，但在任何时间点均未观察到其浸润坏死肌纤维。使用单克隆抗dMHC抗体的免疫组化和免疫印迹显示，恢复负重4天和7天后，表达dMHC异构体的肌纤维比例更高。这些发现表明，巨噬细胞亚群与后肢悬吊恢复过程中的不同阶段相关：ED1+巨噬细胞与肌肉坏死相关，而ED2+细胞与肌肉再生相关。（摘要截选至250词）
