Hypothalamic oxytocin mediates adaptation mechanism against chronic stress in rats.
Hypothalamic oxytocin mediates adaptation mechanism against chronic stress in rats.
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DOI：
10.1152/ajpgi.00483.2009
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发表时间：
2010-10
期刊：
影响因子：
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通讯作者：
Jun Zheng;R. Babygirija;M. Bülbül;Diana Cerjak;K. Ludwig;Toku Takahashi
中科院分区：
文献类型：
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作者：
Jun Zheng;R. Babygirija;M. Bülbül;Diana Cerjak;K. Ludwig;Toku Takahashi
持续生活压力（慢性压力）的积累往往会导致胃部症状。虽然中枢催产素具有抗应激作用，但中枢催产素在应激诱导的胃动力障碍中的作用仍不清楚。在接受急性束缚应激、连续5天重复束缚应激（慢性同型应激）和连续7天不同类型应激（慢性异型应激）的大鼠中测量固体胃排空。侧脑室注射催产素和催产素受体拮抗剂。实时荧光定量RT-PCR检测下丘脑室旁核（PVN）促肾上腺皮质激素释放因子（CRF）mRNA和催产素mRNA的表达。免疫组织化学方法观察室旁核催产素能神经元的变化。急性应激使胃排空延迟，连续5天慢性同型应激后，胃排空延迟完全恢复。相反，慢性异型应激后胃排空延迟持续存在。脑室内注射催产素拮抗剂可拮抗慢性同型应激后胃排空的恢复。下腔静脉注射催产素可恢复慢性异型应激所致的胃排空延迟。CRF mRNA表达在急性应激和慢性异型应激时显著增加，在慢性同型应激后恢复到基础水平。与此相反，催产素mRNA的表达显着增加慢性同型应激。催产素免疫反应细胞的数量增加，慢性同型应激后在PVN的大细胞部分。脑室内注射催产素可降低急性应激和慢性异型应激诱导的CRF mRNA表达。提示慢性应激的适应机制可能与下丘脑催产素表达上调有关，而下丘脑催产素表达上调又减弱了CRF的表达。
Accumulation of continuous life stress (chronic stress) often causes gastric symptoms. Although central oxytocin has antistress effects, the role of central oxytocin in stress-induced gastric dysmotility remains unknown. Solid gastric emptying was measured in rats receiving acute restraint stress, 5 consecutive days of repeated restraint stress (chronic homotypic stress), and 7 consecutive days of varying types of stress (chronic heterotypic stress). Oxytocin and oxytocin receptor antagonist were administered intracerebroventricularly (icv). Expression of corticotropin-releasing factor (CRF) mRNA and oxytocin mRNA in the paraventricular nucleus (PVN) of the hypothalamus was evaluated by real-time RT-PCR. The changes of oxytocinergic neurons in the PVN were evaluated by immunohistochemistry. Acute stress delayed gastric emptying, and the delayed gastric emptying was completely restored after 5 consecutive days of chronic homotypic stress. In contrast, delayed gastric emptying persisted following chronic heterotypic stress. The restored gastric emptying following chronic homotypic stress was antagonized by icv injection of an oxytocin antagonist. Icv injection of oxytocin restored delayed gastric emptying induced by chronic heterotypic stress. CRF mRNA expression, which was significantly increased in response to acute stress and chronic heterotypic stress, returned to the basal levels following chronic homotypic stress. In contrast, oxytocin mRNA expression was significantly increased following chronic homotypic stress. The number of oxytocin-immunoreactive cells was increased following chronic homotypic stress at the magnocellular part of the PVN. Icv injection of oxytocin reduced CRF mRNA expression induced by acute stress and chronic heterotypic stress. It is suggested that the adaptation mechanism to chronic stress may involve the upregulation of oxytocin expression in the hypothalamus, which in turn attenuates CRF expression.