Zeta Inhibitory Peptide as a Novel Therapy to Control Chronic Visceral Hypersensitivity in a Rat Model.
Zeta Inhibitory Peptide as a Novel Therapy to Control Chronic Visceral Hypersensitivity in a Rat Model.
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Zeta 抑制肽作为控制大鼠模型慢性内脏超敏反应的新疗法
DOI：
10.1371/journal.pone.0163324
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Lin C
中科院分区：
文献类型：
--
作者：
Tang Y;Chen A;Chen Y;Guo L;Dai H;Huang Y;Chen Q;Lin C
背景多种慢性内脏痛综合征，如肠易激综合征（IBS）的发病机制尚不清楚，因此目前的治疗方法无效。本研究旨在探讨脊髓蛋白激酶M zeta（PKM zeta）对IBS大鼠内脏痛敏感性的影响，以更好地了解IBS的发病机制，并探讨zeta抑制肽（ZIP）治疗慢性内脏痛的效果。方法采用新生儿母婴分离法（NMS）建立内脏高敏大鼠模型。内脏痛敏感性通过腹部肌肉对结直肠扩张（CRD）的肌电图（EMG）反应来评估。Western blot检测脊髓PKM β和磷酸化PKM β（p-PKM β）。鞘内注射不同剂量的ZIP，以研究脊髓PKM β在慢性内脏高敏感性中的作用。使用旷场试验来确定ZIP疗法是否引起自发运动活动副作用。结果与对照组相比，分级CRD压力可显著增加NMS大鼠的肌电反应（p < 0.05）。与对照组相比，伴有明显慢性内脏痛的IBS样大鼠胸腰段和腰骶段脊髓中p-PKM β表达增加（p < 0.05）。EMG数据显示，鞘内注射ZIP（1、5和10 μg）剂量依赖性地减轻IBS样大鼠的内脏疼痛超敏性。结论磷酸化PKM β可能参与了IBS大鼠慢性内脏高敏感性的脊髓中枢增敏作用，ZIP治疗慢性内脏痛效果良好。
Background The pathogenesis of multiple chronic visceral pain syndromes, such as irritable bowel syndrome (IBS), is not well known, and as a result current therapies are ineffective. The objective of this study was to investigate the effect of spinal protein kinase M zeta (PKMζ) on visceral pain sensitivity in rats with IBS to better understand the pathogenesis and investigate the effect of zeta inhibitory peptide (ZIP) as a therapy for chronic visceral pain. Methods Visceral hypersensitivity rats were produced by neonatal maternal separation (NMS). Visceral pain sensitivity was assessed by electromyographic (EMG) responses of abdominal muscles to colorectal distention (CRD). Spinal PKMζ and phosphorylated PKMζ (p-PKMζ) were detected by western blot. Varying doses of ZIP were intrathecally administered to investigate the role of spinal PKMζ in chronic visceral hypersensitivity. The open field test was used to determine if ZIP therapy causes spontaneous motor activity side effects. Results Graded CRD pressure significantly increased EMG responses in NMS rats compared to control rats (p < 0.05). p-PKMζ expression increased in the thoracolumbar and lumbosacral spinal cord in the IBS-like rats with notable concomitant chronic visceral pain compared to control rats (p < 0.05). EMG data revealed that intrathecal ZIP injection (1, 5, and 10 μg) dose-dependently attenuated visceral pain hypersensitivity in IBS-like rats. Conclusions Phosphorylated PKMζ may be involved in the spinal central sensitization of chronic visceral hypersensitivity in IBS, and administration of ZIP could effectively treat chronic visceral pain with good outcomes in rat models.
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影响因子：
2.7
作者：
Alstott, Jeff;Timberlake, William
通讯作者：
Timberlake, William
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29.4
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Maneerattanaporn, Monthira;Chey, William D
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4.8
作者：
Hernandez, AI;Blace, N;Sacktor, TC
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3.3
作者：
Marchand F;D'Mello R;Yip PK;Calvo M;Muller E;Pezet S;Dickenson AH;McMahon SB
通讯作者：
McMahon SB
影响因子：
2.5
作者：
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通讯作者：
Lin C