Upregulation of cystathionine beta-synthetase expression by nuclear factor-kappa B activation contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation.
Upregulation of cystathionine beta-synthetase expression by nuclear factor-kappa B activation contributes to visceral hypersensitivity in adult rats with neonatal maternal deprivation.
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DOI：
10.1186/1744-8069-8-89
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发表时间：
2012-12-18
期刊：
影响因子：
3.3
通讯作者：
Xu GY
中科院分区：
文献类型：
--
作者：
Li L;Xie R;Hu S;Wang Y;Yu T;Xiao Y;Jiang X;Gu J;Hu CY;Xu GY
肠易激综合征（IBS）的特征是慢性内脏痛觉过敏（CVH），表现为持续或反复发作的腹痛和排便改变。然而，CVH的发病机制仍不清楚。本研究旨在探讨内源性硫化氢（H2S）产生酶胱硫醚β-合成酶（CBS）和p65核因子-κ B亚基在CVH中的作用。采用新生儿母亲剥夺（NMD）方法，在出生后2-15天的雄性大鼠上建立CVH模型，并在7-15周龄时进行行为学实验。NMD组7~12周结肠神经背根节CBS表达显著增加。CBS表达的这种变化与对结肠直肠扩张（CRD）的内脏运动反应增强的时间过程密切相关，CRD是内脏疼痛的指标。CBS抑制剂AOAA对NMD大鼠产生剂量依赖性的镇痛作用，而对年龄匹配的健康对照大鼠没有影响。AOAA还逆转了结肠支配DRG中观察到的增强的神经元兴奋性。应用氢化钠，供体的H2S，增加兴奋性的结肠支配DRG神经元急性分离健康对照大鼠。鞘内注射NaHS产生急性内脏痛觉过敏。NMD大鼠脑组织中p65蛋白的含量显著高于同龄对照组。鞘内给予PDTC（一种p65抑制剂）可显著降低CBS的表达，并减弱CRD的伤害性反应。目前的结果表明，上调CBS的表达，这是由p65的激活介导的，有助于NMD诱导的CVH。该通路可能是缓解IBS患者CVH的潜在靶点。
Irritable bowel syndrome (IBS) is characterized by chronic visceral hyperalgesia (CVH) that manifested with persistent or recurrent abdominal pain and altered bowel movement. However, the pathogenesis of the CVH remains unknown. The aim of this study was to investigate roles of endogenous hydrogen sulfide (H2S) producing enzyme cystathionine beta-synthetase (CBS) and p65 nuclear factor-kappa B subunits in CVH. CVH was induced by neonatal maternal deprivation (NMD) in male rats on postnatal days 2–15 and behavioral experiments were conducted at the age of 7–15 weeks. NMD significantly increased expression of CBS in colon-innervating DRGs from the 7th to 12th week. This change in CBS express is well correlated with the time course of enhanced visceromoter responses to colorectal distention (CRD), an indicator of visceral pain. Administration of AOAA, an inhibitor of CBS, produced a dose-dependent antinociceptive effect on NMD rats while it had no effect on age-matched healthy control rats. AOAA also reversed the enhanced neuronal excitability seen in colon-innervating DRGs. Application of NaHS, a donor of H2S, increased excitability of colon-innervating DRG neurons acutely dissociated from healthy control rats. Intrathecal injection of NaHS produced an acute visceral hyperalgesia. In addition, the content of p65 in nucleus was remarkably higher in NMD rats than that in age-matched controls. Intrathecal administration of PDTC, an inhibitor of p65, markedly reduced expression of CBS and attenuated nociceptive responses to CRD. The present results suggested that upregulation of CBS expression, which is mediated by activation of p65, contributes to NMD-induced CVH. This pathway might be a potential target for relieving CVH in patients with IBS.
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影响因子：
4.3
作者：
Bian, Zhao-Xiang;Zhang, Man;Sung, Joseph J. Y.
通讯作者：
Sung, Joseph J. Y.
影响因子：
7.4
作者：
Fu ES;Zhang YP;Sagen J;Candiotti KA;Morton PD;Liebl DJ;Bethea JR;Brambilla R
通讯作者：
Brambilla R
影响因子：
2
作者：
Kataoka, H;Horiyama, S;Ito, Y
通讯作者：
Ito, Y
鞘内注射吡咯烷二硫代氨基甲酸酯预防和逆转坐骨神经慢性缩窄性损伤模型大鼠的神经性疼痛
影响因子：
5.1
作者：
Pan, Yun-Dan;Guo, Qu-Lian;Wang, Yun-Jiao
通讯作者：
Wang, Yun-Jiao
影响因子：
3.3
作者：
O'Rielly, D. D.;Loomis, C. W.
通讯作者：
Loomis, C. W.