Hamilton Stephanie M, Bayer Clifford R, Stevens Dennis L, Lieber Richard L, Bryant Amy E
Infectious Diseases Section, Veterans Affairs Medical Center, 500 W. Fort Street, Boise, ID 83702, USA.
J Infect Dis. 2008 Dec 1;198(11):1692-8. doi: 10.1086/593016.
Myonecrosis due to group A streptococci (GAS) often develops at sites of nonpenetrating muscle injury, and nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the severity of these cryptic infections. We have previously shown that GAS bind to vimentin on injured skeletal muscles in vitro. The present study investigated whether vimentin up-regulation in injured muscles in vivo is associated with homing of circulating GAS to the injured site and whether NSAIDs facilitate this process.
M type 3 GAS were delivered intravenously 48 h after eccentric contraction (EC)-induced injury of murine hind-limb muscles. Vimentin gene expression and homing of GAS were followed by real-time reverse-transcriptase polymerase chain reaction and quantitative bacteriology of muscle homogenates, respectively. In separate experiments, ketorolac tromethamine (Toradol) was given 1 h before GAS infusion.
Vimentin was up-regulated approximately 8-fold 48 h after EC. Significantly more GAS were found in moderately injured muscles than in noninjured controls. NSAIDs greatly augmented the number of GAS in injured muscles.
Vimentin may tether circulating GAS to injured muscle, and NSAIDs enhance this process. Strategies targeting the vimentin-GAS interaction may prevent or attenuate GAS myonecrosis. Use of NSAIDs should increase suspicion of cryptic GAS infection in patients with increasing pain at sites of nonpenetrating muscle injury.
A 组链球菌（GAS）所致的肌坏死常发生于非穿透性肌肉损伤部位，非甾体抗炎药（NSAIDs）可能会加重这些隐匿性感染的严重程度。我们之前已表明，GAS 在体外可与受损骨骼肌上的波形蛋白结合。本研究调查了体内受损肌肉中波形蛋白上调是否与循环 GAS 归巢至损伤部位有关，以及 NSAIDs 是否会促进这一过程。
在小鼠后肢肌肉进行离心收缩（EC）诱导损伤 48 小时后静脉注射 3 型 GAS。分别通过实时逆转录聚合酶链反应和肌肉匀浆定量细菌学检测波形蛋白基因表达和 GAS 的归巢情况。在单独的实验中，在注入 GAS 前 1 小时给予酮咯酸氨丁三醇（托拉朵）。
EC 后 48 小时波形蛋白上调约 8 倍。在中度损伤的肌肉中发现的 GAS 明显多于未损伤的对照组。NSAIDs 极大地增加了损伤肌肉中 GAS 的数量。
波形蛋白可能将循环中的 GAS 拴系至受损肌肉，而 NSAIDs 会增强这一过程。针对波形蛋白 - GAS 相互作用的策略可能预防或减轻 GAS 所致的肌坏死。在非穿透性肌肉损伤部位疼痛加剧的患者中，使用 NSAIDs 应增加对隐匿性 GAS 感染的怀疑。
