Department of Surgery, Medical College of Wisconsin and Zablocki VA Medical Center, Milwaukee, WI 53295, USA.
J Neuroendocrinol. 2010 Nov;22(11):1181-6. doi: 10.1111/j.1365-2826.2010.02069.x.
We have recently shown that impaired gastric motility observed in acute restraint stress was restored following repeated restraint stress in mice. Repeated restraint stress up-regulates oxytocin mRNA expression and down-regulates corticotrophin-releasing factor (CRF) mRNA expression at the hypothalamus. Oxytocin knockout mice (OXT-KO) have been widely used to study the central oxytocin signalling pathways in response to various stressors. We studied the effects of acute and repeated restraint stress on solid gastric emptying and hypothalamic CRF mRNA expression in wild-type (WT) and OXT-KO mice. Heterozygous (HZ) parents (B6; 129S-Oxt(tm1Wsy)/J mice) were bred in our animal facility. Male OXT-KO, WT and HZ littermates were used for the study. Solid gastric emptying was measured following acute restraint stress (for 90 min) or repeated restraint stress (for five consecutive days). Expression of CRF mRNA in the paraventricular nucleus (PVN) was measured by real-time reverse transcriptase-polymerase chain reaction. There were no significant differences of gastric emptying in WT (68.4 ± 4.1%, n = 6), HZ (71.8 ± 3.1%, n = 6) and OXT-KO (70.6 ± 3.1%, n = 6) mice in nonstressed conditions. Acute stress significantly delayed gastric emptying in OXT-KO mice (33.10 ± 2.5%, n = 6) WT (39.1 ± 1.1%, n = 6) and HZ mice (35.8 ± 1.2%, n = 6). Following repeated restraint stress loading, gastric emptying was significantly restored in WT (68.3 ± 4.5%, n = 6) and HZ mice (63.1 ± 2.6%, n = 6). By contrast, gastric emptying was still delayed in OXT-KO mice (34.7 ± 1.3%, n = 6) following repeated restraint stress. The increase in CRF mRNA expression at the PVN was much pronounced in OXT-KO mice compared to WT or HZ mice following repeated restraint stress. These findings suggest that central oxytocin plays a pivotal role in mediating the adaptation mechanism following repeated restraint stress in mice.
我们最近发现，在急性束缚应激中观察到的胃动力受损，在小鼠反复束缚应激后得到恢复。反复束缚应激会在上丘脑上调催产素 mRNA 的表达，并下调促肾上腺皮质释放因子（CRF）mRNA 的表达。催产素敲除小鼠（OXT-KO）已被广泛用于研究中枢催产素信号通路对各种应激源的反应。我们研究了急性和反复束缚应激对野生型（WT）和 OXT-KO 小鼠固体胃排空和下丘脑 CRF mRNA 表达的影响。杂合（HZ）父母（B6；129S-Oxt（tm1Wsy）/J 小鼠）在我们的动物设施中繁殖。雄性 OXT-KO、WT 和 HZ 同窝仔鼠用于研究。急性束缚应激（90 分钟）或反复束缚应激（连续 5 天）后测量固体胃排空。实时逆转录-聚合酶链反应测量室旁核（PVN）中 CRF mRNA 的表达。在非应激条件下，WT（68.4±4.1%，n=6）、HZ（71.8±3.1%，n=6）和 OXT-KO（70.6±3.1%，n=6）小鼠的胃排空没有显著差异。急性应激显著延迟了 OXT-KO 小鼠（33.10±2.5%，n=6）、WT（39.1±1.1%，n=6）和 HZ 小鼠（35.8±1.2%，n=6）的胃排空。在反复束缚应激负荷后，WT（68.3±4.5%，n=6）和 HZ 小鼠（63.1±2.6%，n=6）的胃排空明显恢复。相比之下，反复束缚应激后 OXT-KO 小鼠的胃排空仍然延迟（34.7±1.3%，n=6）。与 WT 或 HZ 小鼠相比，反复束缚应激后 OXT-KO 小鼠 PVN 中 CRF mRNA 表达的增加更为明显。这些发现表明，中枢催产素在介导小鼠反复束缚应激后的适应机制中起关键作用。
