Shao Yun-Yun, Guo Yi-Ting, Gao Jian-Ping, Liu Jun-Jin, Chang Zhuang-Peng, Feng Xiao-Juan, Xu Ding, Deng Gui-Feng, Hou Rui-Gang
School of Pharmaceutical, Shanxi Medical University, Taiyuan, Shanxi 030000, China.
Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030000, China.
Evid Based Complement Alternat Med. 2020 Oct 15;2020:7830280. doi: 10.1155/2020/7830280. eCollection 2020.
Postinflammatory irritable bowel syndrome (PI-IBS) is a common functional gastrointestinal disorder, which is characterized by abdominal pain, low-grade inflammation, and visceral hypersensitivity. Shaoyao-Gancao decoction (SGD) has been used to improve the clinical symptoms of abdominal spasmodic pain accompanying acute gastroenteritis, but the underlying therapeutic mechanism has not been fully elucidated. In the present study, a rat model of PI-IBS was established via rectal administration of TNBS. Rats were scored daily for 28 days using disease activity index (DAI). Abdominal withdrawal reflex (AWR) was used to measure the pain threshold. After SGD (6.25, 12.5, and 25 g/kg/d) treatment for 14 days, rat colonic tissue was collected for histopathological grading, enterochromaffin (EC) cell count, and 5-HT content measurement. RT-qPCR and western blot analyses were employed to detect the gene and protein level of tryptophan hydroxylase (TPH), serotonin reuptake transporter (SERT), and transient receptor potential vanilloid 1 (TRPV1). To further validate the effect of SGD on TRPV1, another experiment was performed in cells. The results revealed that visceral hyperalgesia, reflected by increased DAI, AWR, pathological injury score, 5-HT content, and EC cell count in PI-IBS rats, was significantly ameliorated by SGD. In cells, SGD markedly inhibited the expression and function of TRPV1. Moreover, the expression levels of TPH were also repressed by SGD. The findings of the present study indicated that the therapeutic effect of SGD on visceral hyperalgesia may be closely associated with the regulatory role of TRPV1 and 5-HT signaling pathways.
炎症后肠易激综合征(PI-IBS)是一种常见的功能性胃肠疾病,其特征为腹痛、低度炎症和内脏高敏感性。芍药甘草汤(SGD)已被用于改善急性胃肠炎伴发的腹部痉挛性疼痛的临床症状,但其潜在治疗机制尚未完全阐明。在本研究中,通过直肠注射三硝基苯磺酸(TNBS)建立PI-IBS大鼠模型。连续28天每天使用疾病活动指数(DAI)对大鼠进行评分。采用腹部回撤反射(AWR)来测量疼痛阈值。SGD(6.25、12.5和25 g/kg/d)治疗14天后,收集大鼠结肠组织进行组织病理学分级、肠嗜铬(EC)细胞计数及5-羟色胺(5-HT)含量测定。采用逆转录-定量聚合酶链反应(RT-qPCR)和蛋白质免疫印迹分析来检测色氨酸羟化酶(TPH)、5-羟色胺再摄取转运体(SERT)和瞬时受体电位香草酸亚型1(TRPV1)的基因和蛋白水平。为进一步验证SGD对TRPV1的作用,在细胞中进行了另一项实验。结果显示,PI-IBS大鼠中DAI、AWR、病理损伤评分、5-HT含量及EC细胞计数增加所反映的内脏痛觉过敏,被SGD显著改善。在细胞中,SGD显著抑制TRPV1的表达和功能。此外,SGD还抑制TPH的表达水平。本研究结果表明,SGD对内脏痛觉过敏的治疗作用可能与TRPV1和5-HT信号通路的调节作用密切相关。