Wang Yinshu, Dong Ying, Wang Enkang, Meng Yangyang, Bi Zijuan, Sun Shuai, Zhang Chaochao, Fan Haiting, Yuan Jianye
Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Pharmacol. 2020 Sep 11;11:01082. doi: 10.3389/fphar.2020.01082. eCollection 2020.
Irritable bowel syndrome (IBS) is a functional gut disease characterized by visceral hypersensitivity and gut motor dysfunction. Serotonin (5-hydroxytryptamine, 5-HT) is an important enteric neurotransmitter. High levels of 5-HT aggravate IBS symptoms. The serotonin reuptake transporter (SERT) is a membrane-embedded transporter involved in IBS pathogenesis that plays an important role in regulating 5-HT signaling.
We investigated whether gut motor function was altered in SERT-knockout (SERT-KO) rats. Additionally, we sought to determine whether Shugan decoction (SGD), a clinically experienced prescription for the treatment of IBS, exerts regulatory effects on intestinal motility in SERT-KO rats, and attempted to identify the mechanisms involved.
SERT-KO rats were produced by transcription activator-like effector nuclease (TALEN) technology. Fecal pellet output was measured for ten consecutive days to estimate distal colonic motility. Small intestinal motility was measured by charcoal-meal experiments. The colonic and small intestinal muscle contractile activities were measured by organ bath study. Western blot was used to analyze the muscarinic receptor expression in colon tissue.
Compared with that in wild-type (WT) rats, the defecation amount, amplitude of spontaneous contraction, and the tension of ACh-induced contraction of colonic longitudinal smooth muscle in SERT-KO rats were significantly increased. The expression of muscarinic receptor subtype-3 (MR) in the colons of SERT-KO rats was also elevated. SGD can decrease defecation of SERT-KO rats. Moreover, SGD reduced the amplitude of spontaneous contraction, the frequency and tension of ACh-induced contraction of colonic longitudinal smooth muscle, and the expression of MR in the colon in SERT-KO rats.
SERT-KO rats showed increased defecation accompanied by enhanced colonic motility and MR expression. The findings suggest that SGD modifies colonic dysmotility and reduces defecation in SERT-KO rats by down-regulating MR expression in the colon.
肠易激综合征（IBS）是一种功能性肠道疾病，其特征为内脏高敏感性和肠道运动功能障碍。血清素（5-羟色胺，5-HT）是一种重要的肠道神经递质。高水平的5-HT会加重IBS症状。血清素再摄取转运体（SERT）是一种参与IBS发病机制的膜嵌入转运体，在调节5-HT信号传导中起重要作用。
我们研究了SERT基因敲除（SERT-KO）大鼠的肠道运动功能是否发生改变。此外，我们试图确定疏肝汤（SGD），一种治疗IBS的临床经验方，是否对SERT-KO大鼠的肠道蠕动有调节作用，并试图确定其中涉及的机制。
采用转录激活样效应核酸酶（TALEN）技术制备SERT-KO大鼠。连续十天测量粪便颗粒排出量以评估远端结肠运动。通过炭末实验测量小肠运动。通过器官浴研究测量结肠和小肠肌肉的收缩活动。采用蛋白质免疫印迹法分析结肠组织中毒蕈碱受体的表达。
与野生型（WT）大鼠相比，SERT-KO大鼠的排便量、自发收缩幅度以及乙酰胆碱诱导的结肠纵行平滑肌收缩张力均显著增加。SERT-KO大鼠结肠中毒蕈碱受体亚型3（MR）的表达也升高。SGD可减少SERT-KO大鼠的排便。此外，SGD降低了SERT-KO大鼠结肠纵行平滑肌的自发收缩幅度、乙酰胆碱诱导的收缩频率和张力，以及结肠中MR的表达。
SERT-KO大鼠排便增加，同时结肠运动和MR表达增强。研究结果表明，SGD通过下调结肠中MR的表达来改善SERT-KO大鼠的结肠运动障碍并减少排便。
