弓状核内胱硫醚β-合成酶通过PKC的上调和GluN2B磷酸化参与慢性胰腺炎大鼠腹部痛觉过敏（英文）

发布时间：2018-06-09 23:47

本文选题：弓状核 + 慢性胰腺炎　；参考：《生理学报》2016年05期

【摘要】：有报道显示初级感觉神经元中的硫化氢(H2S)参与内脏痛敏的形成,但其在中枢神经系统中的作用却鲜为人知。该研究旨在探讨下丘脑弓状核(arcuate nucleus,ARC)内H2S和其内源性合成酶是否参与慢性胰腺炎(chronic pancreatitis,CP)腹部痛觉过敏及其潜在机制。成年雄性Sprague-Dawley大鼠胰管内注射三硝基苯磺酸(trinitrobenzene sulfonic acid,TNBS)诱导产生CP模型,运用von Frey filament(VFF)评测大鼠腹部对机械刺激的反应频率,运用Western blot检测ARC内蛋白表达水平。TNBS注射4周后ARC内胱硫醚-β-合成酶(cystathionineβ-synthetase,CBS)表达显著上调,而胱硫醚-γ-裂解酶(cystathionine-γ-lyase,CSE)的表达没有明显改变;CP显著提高了NMDA受体Glu N2B亚单位的磷酸化水平,而总Glu N2B不变;CP也显著上调了蛋白激酶Cγ(PKCγ)在ARC的表达。ARC内微量注射CBS的抑制剂O-(羧甲基)羟胺半盐酸盐(AOAA)能显著降低CP大鼠的腹部疼痛,也翻转了CP大鼠ARC中p-Glu N2B和PKCγ的上调;ARC内微量注射Glu N2B抑制剂或PKC特异性抑制剂白屈菜赤碱能显著减轻CP大鼠的腹部痛觉过敏,PKC特异性抑制剂能减少p-Glu N2B表达。总之,以上数据表明,CP引起了ARC内CBS的上调,并可能通过PKCγ介导了Glu N2B的活化,参与CP痛觉过敏。本研究在一定程度上揭示了CP痛觉过敏产生的中枢机制,并有助于发现CP疼痛治疗的新靶标。
[Abstract]:It has been reported that hydrogen sulfide (H _ 2S) in primary sensory neurons is involved in the formation of visceral pain sensitivity, but its role in the central nervous system is not well known. The aim of this study was to investigate whether H _ 2S and its endogenous synthase in the arcuate nucleus arcuate of hypothalamus are involved in abdominal hyperalgesia in chronic pancreatitis (chronic pancreatitis) and its underlying mechanism. Adult male Sprague-Dawley rats were induced to produce CP by intraductal injection of trinitrobenzene sulfonic (TNBs). The frequency of abdominal response to mechanical stimulation was evaluated by von Frey filamentus. The expression of cystathionine 尾 -synthetase (CBS) was significantly up-regulated by Western blot, but the expression of cystathionine- 纬 -lyase (CSE) did not change significantly. The phosphorylation level of Glu N2B subunit of NMDA receptor was significantly increased by CP. Total Glu N2B invariant CP also significantly up-regulated the expression of protein kinase C 纬 -PKC 纬 in ARC. Microinjection of O-carboxymethyl hydroxylamine hemihydrochlorate AOAA into ARC could significantly reduce abdominal pain in CP rats. The up-regulation of p-Glu N2B and PKC 纬 in ARC of CP rats was also reversed. Microinjection of Glu N2B inhibitor or PKC-specific inhibitor of PKC into ARC could significantly reduce the expression of p-Glu N2B in abdominal hyperalgesia of CP rats. In conclusion, the above data suggest that CP may induce the up-regulation of CBS in ARC and may be involved in CP hyperalgesia through PKC 纬 mediated activation of Glu N2B. To some extent, this study reveals the central mechanism of CP hyperalgesia and helps to find new targets for CP pain therapy.
【作者单位】：苏州市疼痛基础研究和临床治疗重点实验室苏州大学神经生物学和生理学系神经科学研究所;
【基金】：supported by grants from the National Natural Science Foundation of China(No.31271258,81230024,81471137 and 31300909) the Science and Technology Development Plan of Suzhou Municipality,Jiangsu Province,China(No.SYS201037 and SYS201102) the Priority Academic Program Development of Jiangsu Higher Education Institutions,Jiangsu Province,China
【分类号】：R576

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