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本研究旨在探讨大鼠中央杏仁核(central amygdala,CeA)内5-HT3受体激动之后,对丝裂原刀豆球蛋白A(concanavalin A,ConA)刺激的胸腺细胞增殖反应的影响,及其潜在的神经内分泌调节环路。分别经大鼠腹腔(intraperitoneal,i．p．)、双侧侧脑室(intracerebroventricle,i．c.v．)和双侧CeA(intracentral amygdala,i.c．a．)注射选择性5-HT3受体激动剂1-phenylbiguanide(PBG),同时制备正常大鼠胸腺细胞悬液与不同浓度FBG(1×10-8～1×10-5mol/L)体外共同孵育。经MTT法测定显示,无论有无ConA刺激,正常大鼠离体胸腺细胞在与PBG(1×10-8～1×10-5mol／L)体外共同孵育时其增殖反应均不受后者影响;PBG i．p．(每天0．5 mg／kg,连续5 d)对ConA刺激的胸腺细胞的增殖反应亦无影响,而PBG i．c.v．(每天10μg/侧,连续5 d)则显著增强之;当PBG i.c．a．(每天1．0μg,侧,1 d或连续3、5、7 d)时,ConA刺激的胸腺细胞的增殖反应于给药后第1天即开始增强且日益显著,第5天达到高峰,第7天则趋于减弱。在给予PBG 5 min前相同给药部位先给予5-HT3受体拮抗剂tropisetron(TRP)预处理可逆转PBG的促胸腺细胞增殖效应。免疫组织化学SABC法检测显示,PBG(1．0μg／侧,i．c．a．)单次给药后各脑区可相继出现大量c-Fos阳性细胞(CeA:1 h;海马及皮层:1～2 h;下丘脑:4 h;中脑导水管周围灰质:8 h),并迅速达到各自高峰(CeA: 1 h;海马及皮层:2 h;下丘脑:4 h),与相应的生理盐水对照组及TRP预处理组相比均有显著性差异。随后,这一表达在各脑区中逐步减弱并消失(CeA:4 h;海马、皮层及下丘脑:8 h)。由此推论,大鼠CeA内5-HT3受体至少可部分通过边缘系统-皮层-下丘脑-中脑导水管周围灰质这一神经内分泌环路调制胸腺细胞功能。
The purpose of this study was to investigate the effect of 5-HT3 receptor activation in the central amygdala (CeA) on the proliferation of thymocytes stimulated by mitogen concanavalin A (ConA) and Its potential neuroendocrine regulatory loop. Selective 5-HT3 receptor agonist 1 was injected intraperitoneal (i.p.), bilateral intracerebroventricle (i.cv.) And bilateral ceA (am. -phenylbiguanide (PBG). Meanwhile, normal rat thymocytes were prepared and incubated with different concentrations of FBG (1 × 10-8 ~ 1 × 10-5mol / L) in vitro. The results of MTT assay showed that the proliferative responses of normal rat thymocytes in vitro incubated with PBG (1 × 10-8 ~ 1 × 10-5mol / L) were not affected by the latter with or without ConA stimulation ; PBG i. p. (0.5 mg / kg daily for 5 consecutive days) had no effect on ConA-stimulated thymocyte proliferation, whereas PBG i. c.v. (10 μg / side per day for 5 consecutive days) was significantly enhanced; when PBG i.c. a. (1.0 μg daily, 1 d daily, or 3, 5, and 7 consecutive days), the proliferative responses of ConA-stimulated thymocytes began to increase and became significant on the first day after administration and reached its peak on the fifth day. 7 days tends to weaken. Pretreatment with the 5-HT3 receptor antagonist tropisetron (TRP) at the same site of administration 5 minutes prior to PBG administration reversed the thymocyte proliferation effect of PBG. Immunocytochemistry SABC assay showed that a large number of c-Fos positive cells (CeA: 1 h; hippocampus and cortex: 1 h after single administration of PBG (1.0 μg / side, i.c.a.) 1 h, 2 h; hypothalamus: 4 h; midbrain periaqueductal gray: 8 h) and rapidly reached their peak (CeA: 1 h; hippocampus and cortex: 2 h; hypothalamus: 4 h) Saline control group and TRP pretreatment group compared with significant differences. Subsequently, this expression gradually weakened and disappeared in various brain regions (CeA: 4 h; hippocampus, cortex and hypothalamus: 8 h). Thus, in conclusion, 5-HT3 receptors in rat CeA modulate thymocyte function at least partially through the neuroendocrine loop of the limbic system-cortex-hypothalamus-midbrain periaqueductal gray.