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川北医学院附属医院中西医结合肛肠科,南充 637000
刘 萌,Email:Lmeng1082@163.com,研究方向:中西医结合肛肠领域。
唐学贵,Email:Txg668nc@sohu.com。
收稿:2024-01-02,
修回:2024-03-26,
录用:2024-04-10,
纸质出版:2024-12-28
移动端阅览
刘萌,徐青霞,朱阳阳,等.四磨汤通过调节TGR5/TRPA1信号通路对慢传输型便秘大鼠肠道动力的影响[J].重庆医科大学学报,2024,49(12):1566-1571.
Liu Meng,Xu Qingxia,Zhu Yangyang,et al.Effect of Simo decoction on intestinal motility in rats with slow transit constipation by regulating the Takeda G protein-coupled receptor 5/transient receptor potential ankyrin 1 signaling pathway[J].Journal of Chongqing Medical University,2024,49(12):1566-1571.
刘萌,徐青霞,朱阳阳,等.四磨汤通过调节TGR5/TRPA1信号通路对慢传输型便秘大鼠肠道动力的影响[J].重庆医科大学学报,2024,49(12):1566-1571. DOI: 10.13406/j.cnki.cyxb.003632.
Liu Meng,Xu Qingxia,Zhu Yangyang,et al.Effect of Simo decoction on intestinal motility in rats with slow transit constipation by regulating the Takeda G protein-coupled receptor 5/transient receptor potential ankyrin 1 signaling pathway[J].Journal of Chongqing Medical University,2024,49(12):1566-1571. DOI: 10.13406/j.cnki.cyxb.003632.
目的
2
四磨汤通过调节胆汁酸G蛋白偶联受体5(G-protein coupled-receptor kinase5,TGR5)/瞬时受体电位锚蛋白1(transient receptor potential ankyrin-1,TRPA1)信号通路对慢传输型便秘(slow transit constipation,STC)大鼠肠道动力的影响。
方法
2
取SD大鼠采用复方地芬诺酯混悬液灌胃法制备STC模型,随机分为模型组、四磨汤低剂量(1.8 g/kg)组、四磨汤高剂量(3.6 g/kg)组、四磨汤高剂量(3.6 g/kg)+SBI-115(TGR5抑制剂,55.4 mg/kg)组,每组10只,另取10只SD大鼠灌胃等剂量生理盐水设为对照组,采用四磨汤与SBI-115分组处理后测量各组大鼠首粒黑便排出时间、6 h内排便粒数及排便重量、小肠炭末推进率、结肠平滑肌收缩力;以苏木精-伊红(hematoxylin eosin,HE)染色检测各组大鼠结肠病理形态;以免疫组织化学染色检测各组大鼠结肠组织受体5-羟色胺受体3(5-hydroxytryptamine receptor 3,5-HT3R)表达;以酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)试剂盒测量各组大鼠结肠组织5-羟色胺(5-hydroxytryptamine,5-HT)与炎症因子白细胞介素(interleukin,IL)-6、IL-1β水平;以免疫印迹法检测各组大鼠结肠组织TGR5/TRPA1通路蛋白表达。
结果
2
与对照组比较,模型组大鼠结肠组织发生明显病理损伤,首粒黑便排出时间、结肠组织IL-6及IL-1β水平明显升高(
P
<
0.05),6 h内排便粒数、排便重量、小肠炭末推进率、结肠平滑肌收缩力、结肠组织5-HT3R阳性表达、5-HT水平及TGR5、TRPA1蛋白表达明显降低(
P
<
0.05);与模型组比较,四磨汤低剂量组、四磨汤高剂量组大鼠结肠组织病理损伤均减轻,首粒黑便排出时间、结肠组织IL-6及IL-1β水平均降低(
P
<
0.05),6 h内排便粒数、排便重量、小肠炭末推进率、结肠平滑肌收缩力、结肠组织5-HT3R阳性表达、5-HT水平及TGR5、TRPA1蛋白表达均升高(
P
<
0.05),且高剂量四磨汤作用更强;SBI-115可减弱四磨汤对STC大鼠各指标的作用。
结论
2
四磨汤可通过促进TGR5/TRPA1信号活化而抑制STC大鼠结肠炎症,升高大鼠结肠组织5-HT水平及其受体5-HT3R表达,减轻大鼠结肠组织病理损伤,进而增强大鼠结肠平滑肌收缩力及肠道动力,减轻其便秘症状。
Objective
2
To investigate the effect of Simo decoction on intestinal motility in rats with slow transit constipation(STC) by regulating the Takeda G protein-coupled receptor 5(TGR5)/transient receptor potential ankyrin 1(TRPA1) signaling pathway.
Methods
2
Sprague-Dawley rats were given compound diphenoxylate suspension by gavage to establish a model of STC,and then they were randomly divided into model group,low-dose(1.8 g/kg) Simo decoction group,high-dose(3.6 g/kg) Simo decoction group,and high-dose(3.6 g/kg) Simo decoction+SBI-115(TGR5 inhibitor,55.4 mg/kg) group,with 10 rats in each group; another 10 rats were given an equal volume of normal saline by gavage and were selected as control group. After treatment with Simo decoction and SBI-115,the rats in each group were measured in terms of the time to first black stool defecation,the number and weight of feces granules within 6 hours,small intestine charcoal powder propulsion rate,and colonic smooth muscle contractibility; HE staining was used to observe colon pathomorphology; immunohistochemical staining was used to measure the expression level of 5-hydroxytryptamine receptor 3(5-HT3R) in colon tissue; ELISA was used to measure the levels of 5-hydroxytryptamine(5-HT) and the inflammatory factors interleukin-6(IL-6) and interleukin-1β(IL-1β) in colon tissue; Western blotting was used to measure the expression of TGR5/TRPA1 pathway proteins in colon tissue.
Results
2
Compared with the control group,the model group had marked pathological damage of colon tissue,significant increases in the time to first black stool defecation and the levels of IL-6 and IL-1β in colon tissue(
P
<
0.05),and significant reductions in the number and weight of feces granules within 6 hours,small intestine charcoal powder propulsion rate,colonic smooth muscle contractibility,positive expression of 5-HT3R in colonic tissue,5-HT level,and the protein expression levels of TGR5 and TRPA1(
P
<
0.05). Compared with the model group,the low- and high-dose Simo decoction groups had alleviation of the pathological damage of colon tissue,significant reductions in the time to first black stool defecation and the levels of IL-6 and IL-1β in colon tissue(
P
<
0.05),and significant increases in the number and weight of feces granules within 6 hours,small intestine charcoal powder propulsion rate,colonic smooth muscle contractibility,positive expression of 5-HT3R in colonic tissue,5-HT level,and the protein expression levels of TGR5 and TRPA1(
P
<
0.05),and high-dose Simo decoction showed a stronger effect. SBI-115 could weaken the effect of high-dose Simo decoction on various indicators of STC rats.
Conclusion
2
Simo decoction can inhibit colitis in STC rats by promoting the activation of TGR5/TRPA1 signaling,increase the levels of 5-HT and its receptor 5-HT3R in rat colon tissue,and alleviate pathological damage of colon tissue,thereby enhancing the contractibility of colon smooth muscle and intestinal motility and alleviating the symptoms of constipation.
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