Abstract：
It has been reported that the clinical symptoms of functional dyspepsia (FD) exacerbate upon stress while the gender-related factors have been incompletely understood. This study aims to investigate the role of sex in chronic heterotypic stress (CHS)-induced autonomic and gastric motor dysfunction. For CHS, the rats were exposed to the combination of different stressors for 7 consecutive days. Subsequently, electrocardiography was recorded in anesthetized rats to evaluate heart rate variability (HRV) for the determination of autonomic outflow and sympathovagal balance. Solid gastric emptying (GE) was measured in control and CHS-loaded male and female rats. The immunoreactivities of catecholaminergic cell marker tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), corticotropin releasing factor (CRF), and estrogen receptor (ER-α/β) were evaluated in medullary and pontine brainstem sections by immunohistochemistry. Compared with the controls, CHS significantly delayed GE in males but not in females. There was no significant sex-related difference in parasympathetic indicator HF under either control or CHS conditions. Sympathetic indicator LF was significantly higher in control females compared to the males. The higher sympathetic output in females was found to be attenuated upon CHS; in contrast, the elevated sympathetic output was detected in CHS-loaded males. No sex- or stress-related effect was observed on ChAT immunoreactivity in the dorsal motor nucleus of N.vagus (DMV). In males, greater number of TH-ir cells was observed in the caudal locus coeruleus (LC), while they were more densely detected in the rostral LC of females. Regardless of sex, CHS elevated immunoreactivity of TH throughout the LC. Under basal conditions, greater number of TH-ir cells was detected in the rostral ventrolateral medulla (RVLM) of females. In contrast, CHS remarkably increased the number of TH-ir cells in the RVLM of males which was found to be decreased in females. There was no sex-related alteration in TH immunoreactivity in the nucleus tractus solitarius (NTS) of control rats, while CHS affected both sexes in a similar manner. Compared with females, CRF immunoreactivity was prominently observed in control males, while both of which were stimulated by CHS. ER-α/β was found to be co-expressed with TH in the NTS and LC which exhibit no alteration related to either sex or stress status. These results indicate a sexual dimorphism in the catecholaminergic and the CRF system in brainstem which might be involved in the CHS-induced autonomic and visceral dysfunction occurred in males.
摘要：
据报道，功能性消化不良（FD）的临床症状在压力下会加剧，而性别相关因素尚未完全了解。本研究旨在探讨性别在慢性异型应激（CHS）引起的自主神经和胃运动功能障碍中的作用。对于CHS，大鼠连续7天暴露于不同应激源的组合。随后，在麻醉大鼠中记录心电图以评估心率变异性（HRV），以确定自主神经流出和交感神经平衡。在对照和CHS负载的雄性和雌性大鼠中测量固体胃排空(GE)。儿茶酚胺能细胞标记酪氨酸羟化酶（TH）的免疫反应性，胆碱乙酰转移酶（ChAT），促肾上腺皮质激素释放因子（CRF），通过免疫组织化学评估髓质和脑桥脑干切片中的雌激素受体（ER-α/β）。与对照组相比，CHS显着延迟了男性的GE，但未延迟女性的GE。在控制或CHS条件下，副交感神经指标HF均无明显的性别相关差异。与男性相比，对照组女性的交感神经指标LF明显更高。发现女性较高的交感神经输出在CHS后减弱；相比之下，在患有CHS的男性中检测到交感神经输出升高。在迷走神经念珠菌（DMV）的背侧运动核中，未观察到与性别或压力相关的作用。在男性中，在尾端蓝斑（LC）中观察到更多的TH-ir细胞，而它们在女性的前端LC中被更密集地检测到。不管性别,CHS提高了整个LC中TH的免疫反应性。在基础条件下，在雌性延髓头端腹外侧（RVLM）中检测到更多的TH-ir细胞。相比之下,CHS显着增加了雄性RVLM中TH-ir细胞的数量，而雌性则减少了。对照大鼠孤束核（NTS）的TH免疫反应性没有性别相关的改变，而CHS以相似的方式影响两性。与女性相比，CRF免疫反应性在对照男性中显著观察到，而两者都是由CHS刺激的。发现ER-α/β在NTS和LC中与TH共表达,其没有表现出与性别或应激状态相关的改变。这些结果表明，儿茶酚胺能和脑干CRF系统存在性二态性，这可能与CHS引起的男性自主神经和内脏功能障碍有关。
