Wang Lixin, Mogami Sachiko, Yakabi Seiichi, Karasawa Hiroshi, Yamada Chihiro, Yakabi Koji, Hattori Tomohisa, Taché Yvette
CURE/Digestive Diseases Center and Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division, University of California at Los Angeles, and VA Greater Los Angeles Health Care System, Los Angeles, California, United States of America.
Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki, Japan.
PLoS One. 2015 Sep 30;10(9):e0139325. doi: 10.1371/journal.pone.0139325. eCollection 2015.
Abdominal surgery inhibits food intake and induces c-Fos expression in the hypothalamic and medullary nuclei in rats. Rikkunshito (RKT), a Kampo medicine improves anorexia. We assessed the alterations in meal microstructure and c-Fos expression in brain nuclei induced by abdominal surgery and the modulation by RKT in mice. RKT or vehicle was gavaged daily for 1 week. On day 8 mice had no access to food for 6-7 h and were treated twice with RKT or vehicle. Abdominal surgery (laparotomy-cecum palpation) was performed 1-2 h before the dark phase. The food intake and meal structures were monitored using an automated monitoring system for mice. Brain sections were processed for c-Fos immunoreactivity (ir) 2-h after abdominal surgery. Abdominal surgery significantly reduced bouts, meal frequency, size and duration, and time spent on meals, and increased inter-meal interval and satiety ratio resulting in 92-86% suppression of food intake at 2-24 h post-surgery compared with control group (no surgery). RKT significantly increased bouts, meal duration and the cumulative 12-h food intake by 11%. Abdominal surgery increased c-Fos in the prelimbic, cingulate and insular cortexes, and autonomic nuclei, such as the bed nucleus of the stria terminalis, central amygdala, hypothalamic supraoptic (SON), paraventricular and arcuate nuclei, Edinger-Westphal nucleus (E-W), lateral periaqueduct gray (PAG), lateral parabrachial nucleus, locus coeruleus, ventrolateral medulla and nucleus tractus solitarius (NTS). RKT induced a small increase in c-Fos-ir neurons in the SON and E-W of control mice, and in mice with surgery there was an increase in the lateral PAG and a decrease in the NTS. These findings indicate that abdominal surgery inhibits food intake by increasing both satiation (meal duration) and satiety (meal interval) and activates brain circuits involved in pain, feeding behavior and stress that may underlie the alterations of meal pattern and food intake inhibition. RKT improves food consumption post-surgically that may involve modulation of pain pathway.
腹部手术会抑制大鼠的食物摄入，并诱导下丘脑和延髓核中c-Fos的表达。汉方药物六君子汤（RKT）可改善食欲不振。我们评估了腹部手术诱导的小鼠进食微观结构和脑核中c-Fos表达的变化，以及RKT对其的调节作用。连续1周每天给小鼠灌胃RKT或赋形剂。在第8天，小鼠禁食6-7小时，并用RKT或赋形剂处理两次。在黑暗期前1-2小时进行腹部手术（剖腹术-盲肠触诊）。使用小鼠自动监测系统监测食物摄入量和进食结构。腹部手术后2小时，对脑切片进行c-Fos免疫反应性（ir）处理。与对照组（未手术）相比，腹部手术显著减少了进食次数、进餐频率、进食量和持续时间以及进食时间，增加了进餐间隔和饱腹感，导致术后2-24小时食物摄入量抑制92-86%。RKT显著增加了进食次数、进餐持续时间和12小时累积食物摄入量的11%。腹部手术增加了前边缘区、扣带回和岛叶皮质以及自主神经核中的c-Fos，如终纹床核、中央杏仁核、下丘脑视上核（SON）、室旁核和弓状核以及动眼神经副核（E-W）、外侧导水管周围灰质（PAG）、外侧臂旁核、蓝斑、延髓腹外侧和孤束核（NTS）。RKT在对照组小鼠的SON和E-W以及手术小鼠的外侧PAG中诱导c-Fos-ir神经元有小幅增加，而在NTS中有减少。这些发现表明，腹部手术通过增加饱腹感（进餐持续时间）和饱足感（进餐间隔）来抑制食物摄入，并激活参与疼痛、进食行为和应激的脑回路，这可能是进餐模式改变和食物摄入抑制的基础。RKT改善术后食物消耗，这可能涉及对疼痛通路的调节。
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