Abstract：
BACKGROUND: Irritable Bowel Syndrome (IBS) is a prevalent gastrointestinal disorder that significantly diminishes the quality of life for affected individuals. The pathophysiology of IBS remains poorly understood, and available therapeutic options for IBS are limited. The crucial roles of brain-gut interaction, which is mediated by the Hypothalamic-Pituitary-Adrenocortical (HPA) axis and the autonomic nervous system in IBS, have attracted increasing attention.
OBJECTIVE: The objective of this study was to examine the impact of paeoniflorin (PF) on anxiety and visceral hypersensitivity in maternal separation-induced IBS-like rats.
METHODS: The IBS-like rat model was established through the implementation of Maternal Separation (MS) and subsequently subjected to various doses of PF administered via oral gavage for 14 days. Anxiety-like behavior was evaluated using the Open Field Test (OFT) and Elevated Plus Maze (EPM) test. The assessment of visceral sensitivity involved the utilization of the Abdominal Withdrawal Reflex (AWR) score and electromyographic (EMG) responses of the external oblique muscle in response to colorectal distention. The levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), and corticotrophin-releasing hormone (CRH) were examined by ELISA. Quantitative real-time PCR (qRT-PCR) and immunofluorescence were employed to detect the expressions of CRH receptors 1 (CRHR1) and 2 (CRHR2). Glucocorticoid receptors (GR), mineralocorticoid receptor (MR), brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and phospholipase C γ1 (PLCγ1) were examined by Western blot.
CONCLUSIONS: The results showed that MS induced anxiety-like behavior and visceral hypersensitivity, while PF treatment attenuated these changes. Furthermore, the HPA axis hyperactivity in MS rats was attenuated by PF treatment, indicated by reduced serum ACTH, CORT, and CRH levels and recovered hippocampal CRHR1 and GR expressions. In addition, PF inhibited BDNF/TrkB signaling by downregulating the protein levels of BDNF, TrkB, and phospho-PLCγ1 in the colon.
CONCLUSIONS: These findings suggest that PF alleviated anxiety and visceral hypersensitivity in MS-induced IBS-like rats, which may be the modulation of HPA axis activity and BDNF/TrkB/PLCγ1 signaling pathway.
OBJECTIVE: The objective of this study was to examine the impact of paeoniflorin (PF) on anxiety and visceral hypersensitivity in maternal separation-induced IBS-like rats.
METHODS: The IBS-like rat model was established through the implementation of Maternal Separation (MS) and subsequently subjected to various doses of PF administered via oral gavage for 14 days. Anxiety-like behavior was evaluated using the Open Field Test (OFT) and Elevated Plus Maze (EPM) test. The assessment of visceral sensitivity involved the utilization of the Abdominal Withdrawal Reflex (AWR) score and electromyographic (EMG) responses of the external oblique muscle in response to colorectal distention. The levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), and corticotrophin-releasing hormone (CRH) were examined by ELISA. Quantitative real-time PCR (qRT-PCR) and immunofluorescence were employed to detect the expressions of CRH receptors 1 (CRHR1) and 2 (CRHR2). Glucocorticoid receptors (GR), mineralocorticoid receptor (MR), brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and phospholipase C γ1 (PLCγ1) were examined by Western blot.
CONCLUSIONS: The results showed that MS induced anxiety-like behavior and visceral hypersensitivity, while PF treatment attenuated these changes. Furthermore, the HPA axis hyperactivity in MS rats was attenuated by PF treatment, indicated by reduced serum ACTH, CORT, and CRH levels and recovered hippocampal CRHR1 and GR expressions. In addition, PF inhibited BDNF/TrkB signaling by downregulating the protein levels of BDNF, TrkB, and phospho-PLCγ1 in the colon.
CONCLUSIONS: These findings suggest that PF alleviated anxiety and visceral hypersensitivity in MS-induced IBS-like rats, which may be the modulation of HPA axis activity and BDNF/TrkB/PLCγ1 signaling pathway.
摘要：
背景：肠易激综合征（IBS）是一种普遍的胃肠道疾病，显着降低受影响个体的生活质量。IBS的病理生理学仍然知之甚少，和IBS可用的治疗选择是有限的。脑-肠相互作用的关键作用，它是由下丘脑-垂体-肾上腺皮质（HPA）轴和自主神经系统介导的，引起了越来越多的关注。
目的：本研究的目的是研究芍药苷（PF）对母系分离诱导的IBS样大鼠焦虑和内脏高敏感性的影响。
方法：通过实施母体分离（MS）建立IBS样大鼠模型，然后通过口服灌胃给药进行14天的各种剂量的PF。使用开场测试(OFT)和高架迷宫(EPM)测试评价焦虑样行为。内脏敏感性的评估涉及利用腹部戒断反射（AWR）评分和外斜肌的肌电图（EMG）反应对结直肠扩张的反应。促肾上腺皮质激素（ACTH）的水平，皮质酮（CORT），用ELISA法检测促肾上腺皮质激素释放激素(CRH)。采用实时定量PCR（qRT-PCR）和免疫荧光检测CRH受体1（CRHR1）和2（CRHR2）的表达。糖皮质激素受体(GR),盐皮质激素受体（MR），脑源性神经营养因子(BDNF),酪氨酸受体激酶B(TrkB),通过蛋白质印迹检测磷脂酶Cγ1（PLCγ1）。
结论：结果显示MS可诱发焦虑样行为和内脏高敏感性，而PF治疗减弱了这些变化。此外，通过PF治疗减轻MS大鼠的HPA轴过度活跃，血清ACTH降低，CORT,和CRH水平，海马CRHR1和GR表达恢复。此外,PF通过下调BDNF的蛋白水平来抑制BDNF/TrkB信号传导,TrkB,和结肠中的磷酸-PLCγ1。
结论：这些发现表明PF减轻MS诱导的IBS样大鼠的焦虑和内脏高敏感性，可能是调节HPA轴活性和BDNF/TrkB/PLCγ1信号通路。
目的：本研究的目的是研究芍药苷（PF）对母系分离诱导的IBS样大鼠焦虑和内脏高敏感性的影响。
方法：通过实施母体分离（MS）建立IBS样大鼠模型，然后通过口服灌胃给药进行14天的各种剂量的PF。使用开场测试(OFT)和高架迷宫(EPM)测试评价焦虑样行为。内脏敏感性的评估涉及利用腹部戒断反射（AWR）评分和外斜肌的肌电图（EMG）反应对结直肠扩张的反应。促肾上腺皮质激素（ACTH）的水平，皮质酮（CORT），用ELISA法检测促肾上腺皮质激素释放激素(CRH)。采用实时定量PCR（qRT-PCR）和免疫荧光检测CRH受体1（CRHR1）和2（CRHR2）的表达。糖皮质激素受体(GR),盐皮质激素受体（MR），脑源性神经营养因子(BDNF),酪氨酸受体激酶B(TrkB),通过蛋白质印迹检测磷脂酶Cγ1（PLCγ1）。
结论：结果显示MS可诱发焦虑样行为和内脏高敏感性，而PF治疗减弱了这些变化。此外，通过PF治疗减轻MS大鼠的HPA轴过度活跃，血清ACTH降低，CORT,和CRH水平，海马CRHR1和GR表达恢复。此外,PF通过下调BDNF的蛋白水平来抑制BDNF/TrkB信号传导,TrkB,和结肠中的磷酸-PLCγ1。
结论：这些发现表明PF减轻MS诱导的IBS样大鼠的焦虑和内脏高敏感性，可能是调节HPA轴活性和BDNF/TrkB/PLCγ1信号通路。
