目的 探究CaMKⅣ信号对肌纤维功能及肌内炎症的影响。 方法 选择野生C57BL/6 鼠(对照)、CaMKⅣ敲除鼠(CaMKⅣ-/-)。Cardiotoxin(CTX)胫骨前肌(TA)注射诱导小鼠急性肌损伤。比较两组动物损伤肌内肌纤维的修复速度、肌内炎症细胞浸润。体外分化培养原代WT,或CaMKⅣ-/- 成肌细胞(MPCs),与巨噬细胞共培养,对比分析巨噬细胞功能差异。 结果 与WT鼠相比,CaMKⅣ-/-鼠损伤肌肌再生延迟、炎性浸润显著,以M1巨噬细胞为主,M2细胞数量、增殖比例显著下调。体外炎性环境中,CaMKⅣ-/--MPCs共培养体系中的M2巨噬细胞数量与增殖比例较之WT- MPCs均显著下调(P<0.05)。 结论 内源CaMKⅣ信号活化肌纤维参与调控巨噬细胞表型,可促进损伤肌内M2型巨噬细胞增殖分化,有助于炎症撤退,加快肌修复。
Abstract
Objective To investigate the effects of CaMKⅣ signaling on muscle fiber function and intramuscular inflammation. Methods Wild C57BL/6 mice (control group) and CaMKⅣ knockout mice (CaMKⅣ-/-) were selected. Cardiotoxin (CTX) was injected into the anterior tibial muscle to induce acute muscle injury in mice. The repair speed of injured muscle fibers and the infiltration of inflammatory cells in the muscle were compared between the two groups of animals. Primary WT or CaMKⅣ-/- myogenic progenitor cells (MPCs) were differentiated and cultured in vitro, and co-cultured with macrophages. The functional differences of macrophages were compared. Results Compared with WT mice, CaMKⅣ-/- mice had delayed muscle fiber regeneration and significant inflammatory infiltration, mainly dominated by M1 macrophages, with significantly decreased M2 cell numbers and proliferation ratios. In the inflammatory environment in vitro, the number and proliferation ratio of M2 macrophages in the CaMKⅣ-/-- MPCs co-culture system were significantly lower than those in the WT-MPCs (P<0.05). Conclusions The endogenous CaMKⅣ signaling activates muscle fibers to participate in regulating the phenotype of macrophages, promoting the proliferation and differentiation of M2-type macrophages in the injured muscle, facilitating inflammation resolution and accelerating muscle repair.
关键词
CaMKⅣ /
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巨噬细胞胞 /
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炎症 /
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肌纤维
Key words
CaMKⅣ /
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Macrophages /
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Inflammation /
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Muscle fibers
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基金
广东省自然科学基金(2025A1515011221)