Comparison of neurotoxic potency between a novel chinbotulinumtoxinA with onabotulinumtoxinA, incobotulinumtoxinA and lanbotulinumtoxinA in rats.
Comparison of neurotoxic potency between a novel chinbotulinumtoxinA with onabotulinumtoxinA, incobotulinumtoxinA and lanbotulinumtoxinA in rats.
复制标题
新型 chinbotulinumtoxinA 与 onabotulinumtoxinA、incobotulinumtoxinA 和 lanbotulinumtoxinA 对大鼠的神经毒性效力比较
DOI：
10.2147/dddt.s138489
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Jin L
中科院分区：
文献类型：
--
作者：
Feng Y;Liu W;Pan L;Jiang C;Zhang C;Lu Y;Nie Z;Jin L
本研究应用了四种A型肉毒毒素（BoNT/A）产品：onabotulinumtoxinA（A/Ona）、incobotulinumtoxinA（A/Inco）、lanbotulinumtoxinA（A/Lan）和chinbotulinumtoxinA（A/Chin），其中A/Chin为新产品。我们的目的是比较这些毒素的神经毒性效力的肌肉力量减少的衡量标准。此外，还探讨了潜在的分子和细胞机制。根据我们的数据，在注射1周后，四个毒素组的肌肉力量都显著降低。与其他三种产品相比，A/Chin在0.5U剂量下实现了最明显的肌肉力量降低。但当毒素浓度增加到2U时，四种毒素的浓度没有差异。随着毒素逐渐消失，肌肉力量在注射后12周恢复到基础水平。我们进一步测量了参与神经肌肉接头稳定和肌肉发生的关键因子的表达水平。我们的研究结果表明，烟碱乙酰胆碱受体，生肌调节因子和肌肉特异性受体酪氨酸激酶都显着上调后BoNT/A治疗。与肌肉力量的结果一致，A/Chin对基因表达的诱导作用最明显。此外，我们还发现了BoNT/A注射后的局部炎症反应。由于缺乏复合蛋白，与A/Ona和A/Lan组相比，A/Inco和A/Chin均刺激相对较轻的炎症。总之，我们的研究为新型A/Chin的有效性及其与A/Ona，A/Inco和A/Lan相似的功能模式提供了证据。此外，A/Chin在诱导肌肉麻痹和炎症刺激方面具有优势，这可能表明这种新的A/Chin起效更快，持续时间更长。
Four botulinumtoxin type A (BoNT/A) products, onabotulinumtoxinA (A/Ona), incobotulinumtoxinA (A/Inco), lanbotulinumtoxinA (A/Lan) and chinbotulinumtoxinA (A/Chin), are applied in the present study, among which A/Chin is newly produced. We aimed to compare the neurotoxic potency of these toxins by the gauge of muscle strength reduction. Furthermore, potential molecular and cellular mechanisms were also explored. According to our data, muscle strengths in the four toxin groups were all significantly decreased after injection for 1 week. A/Chin achieved the most obvious reduction in muscle strength as compared to the other three products at the dose of 0.5 U. However, there was no difference between the four toxins when increased to 2 U. As the toxins wore off, muscle strength recovered to basal level 12 weeks postinjection. We further measured the expression levels of key factors involved in neuromuscular junction stabilization and muscle genesis. Our results showed that nicotinic acetylcholine receptor, myogenic regulatory factors and muscle-specific receptor tyrosine kinase were all significantly upregulated upon BoNT/A treatment. Consistent with the result of muscle strength, A/Chin had the most obvious induction of gene expression. Moreover, we also found local inflammation response following BoNT/A injection. Owing to lack of complexing proteins, both A/Inco and A/Chin stimulated relatively lighter inflammation compared to that of A/Ona and A/Lan groups. In conclusion, our study provided evidence for the efficacy of the novel A/Chin and its similar functional mode to that of A/Ona, A/Inco and A/Lan. In addition, A/Chin has superiority in inducing muscle paralysis and inflammation stimulation, which may indicate faster onset and longer duration of this novel A/Chin.