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Abstract：
Abnormal expression and distribution of nicotinic acetylcholine receptors (nAChRs) in skeletal muscle caused by sepsis can lead to neuromuscular dysfunction. Here, we asked whether neural agrin regulates nAChRs to ameliorate muscle function, which could be associated with the agrin/muscle-specific kinase pathway.
Rats were subjected to cecal ligation and puncture (CLP) group, sham group, or control group to observe the alteration caused by sepsis. To verify the effect of improving function, rats were injected with agrin or normal saline intramuscularly after CLP. Electromyogram was used to measure neuromuscular function. Cytokines levels of serum and the expression of related proteins and mRNA were tested after treatment.
Compared with the rats in control or sham group, CLP-treated rats showed an acute inflammatory status and a reduction of neuromuscular dysfunction in tibialis anterior muscle, which was associated with abnormal expression in agrin/muscle-specific kinase pathway and increased expression of γ- and α7-nAChR. Exogenous agrin alleviated neuromuscular dysfunction and decreased the expression of γ- and α7-nAChR through agrin-related signaling pathway.
The decreased expression of agrin may lead to skeletal muscle dysfunction. Early enhancement of intramuscular agrin levels after sepsis may be a potential strategy for the treatment of sepsis-induced muscle dysfunction.
Rats were subjected to cecal ligation and puncture (CLP) group, sham group, or control group to observe the alteration caused by sepsis. To verify the effect of improving function, rats were injected with agrin or normal saline intramuscularly after CLP. Electromyogram was used to measure neuromuscular function. Cytokines levels of serum and the expression of related proteins and mRNA were tested after treatment.
Compared with the rats in control or sham group, CLP-treated rats showed an acute inflammatory status and a reduction of neuromuscular dysfunction in tibialis anterior muscle, which was associated with abnormal expression in agrin/muscle-specific kinase pathway and increased expression of γ- and α7-nAChR. Exogenous agrin alleviated neuromuscular dysfunction and decreased the expression of γ- and α7-nAChR through agrin-related signaling pathway.
The decreased expression of agrin may lead to skeletal muscle dysfunction. Early enhancement of intramuscular agrin levels after sepsis may be a potential strategy for the treatment of sepsis-induced muscle dysfunction.
摘要：
脓毒症引起的骨骼肌烟碱型乙酰胆碱受体（nAChRs）的异常表达和分布可导致神经肌肉功能障碍。这里,我们询问神经凝集素是否调节nAChRs以改善肌肉功能，这可能与凝集素/肌肉特异性激酶途径有关。
大鼠进行盲肠结扎和穿孔（CLP）组，假手术组,或对照组观察脓毒症引起的改变。为了验证改进功能的效果，大鼠CLP后肌内注射agrin或生理盐水。肌电图用于测量神经肌肉功能。治疗后检测血清细胞因子水平以及相关蛋白和mRNA的表达。
与对照组和假手术组大鼠比较，CLP治疗的大鼠表现出急性炎症状态，胫骨前肌神经肌肉功能障碍减少，这与agrin/肌肉特异性激酶途径的异常表达以及γ-和α7-nAChR的表达增加有关。外源性agrin通过agrin相关信号通路减轻神经肌肉功能障碍并降低γ-和α7-nAChR的表达。
agrin的表达降低可能导致骨骼肌功能障碍。脓毒症后早期提高肌内聚集素水平可能是治疗脓毒症引起的肌肉功能障碍的潜在策略。
大鼠进行盲肠结扎和穿孔（CLP）组，假手术组,或对照组观察脓毒症引起的改变。为了验证改进功能的效果，大鼠CLP后肌内注射agrin或生理盐水。肌电图用于测量神经肌肉功能。治疗后检测血清细胞因子水平以及相关蛋白和mRNA的表达。
与对照组和假手术组大鼠比较，CLP治疗的大鼠表现出急性炎症状态，胫骨前肌神经肌肉功能障碍减少，这与agrin/肌肉特异性激酶途径的异常表达以及γ-和α7-nAChR的表达增加有关。外源性agrin通过agrin相关信号通路减轻神经肌肉功能障碍并降低γ-和α7-nAChR的表达。
agrin的表达降低可能导致骨骼肌功能障碍。脓毒症后早期提高肌内聚集素水平可能是治疗脓毒症引起的肌肉功能障碍的潜在策略。
