Inhibiting Matrix Metalloproteinases Protects Evoked Electromyography Amplitudes and Muscle Tension in the Orbicularis Oris Muscle in a Rat Model of Facial Nerve Injury.

Inhibiting Matrix Metalloproteinases Protects Evoked Electromyography Amplitudes and Muscle Tension in the Orbicularis Oris Muscle in a Rat Model of Facial Nerve Injury.
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抑制基质金属蛋白酶可保护面神经损伤大鼠模型中口轮匝肌的诱发肌电振幅和肌张力

DOI:
10.1093/jnen/nlac041
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发表时间:
2022-09-19
影响因子:
3.2
通讯作者:
--
中科院分区:
医学4区
文献类型:
--
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摘要面神经损伤导致神经肌肉接头(NMJ)的退化,并阻断突触前和突触后结构之间的神经传递。基质金属蛋白酶(MMPs)是降解和修饰细胞外基质的酶,在调节NMJ重塑中起关键作用。我们以前证明,MMP 1,MMP 2,MMP 3,MMP 7和MMP 9过表达面神经支配的口轮匝肌面神经损伤后,在大鼠模型。在本研究中,MMP抑制剂prinomastat被给予大鼠面神经损伤后。评估MMP水平、聚集蛋白表达和肌肉特异性激酶(MuSK)磷酸化。诱发肌电图(EEMG)振幅的变化也被记录下来。与对照组相比,普利诺司他组面神经损伤后口轮匝肌中MMP的表达显著减少。抑制MMP的表达可维持聚集蛋白的表达和MuSK的磷酸化,并保护损伤后的NMJ形态。此外,普利诺司他治疗可维持损伤后的EEMG振幅和肌肉张力。这些发现表明,抑制MMPs可以保护NMJ的功能和形态,并证明在面神经损伤后的早期阶段需要保护NMJ。
Abstract Facial nerve injury results in degradation of the neuromuscular junction (NMJ) and blocks neurotransmission between the pre- and postsynaptic structures, which are separated by a synaptic cleft. Matrix metalloproteinases (MMPs), enzymes that degrade and modify the extracellular matrix, play critical roles in regulating NMJ remodeling. We previously demonstrated that MMP1, MMP2, MMP3, MMP7, and MMP9 are overexpressed in facial nerve-innervated orbicularis oris muscle after facial nerve injury in a rat model. In the present study, the MMP inhibitor prinomastat was administered to rats after facial nerve injury. The MMP levels, agrin expression, and muscle-specific kinase (MuSK) phosphorylation were evaluated. Variations in evoked electromyography (EEMG) amplitude were also recorded. Compared with the control group, MMP expression in the orbicularis oris after facial nerve injury was significantly reduced in the prinomastat group. Inhibition of MMP expression maintained agrin expression and MuSK phosphorylation; the NMJ morphology was also protected after the injury. Moreover, prinomastat treatment sustained EEMG amplitude and muscle tension after the injury. These findings indicate that inhibiting MMPs can protect the function and morphology of the NMJ and demonstrate the need for protection of the NMJ at early stages after facial nerve injury.
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