切换至 "中华医学电子期刊资源库"

中华结直肠疾病电子杂志 ›› 2025, Vol. 14 ›› Issue (04) : 345 -352. doi: 10.3877/cma.j.issn.2095-3224.2025.04.006

论著

骶神经电刺激对慢传输型便秘小鼠结肠5-HT4R表达的影响
陈晓瑶1, 李丽2, 孙冰3, 李涛3, 崔萌3, 武国亮3,()   
  1. 1250014 济南,山东第一医科大学第一附属医院(第一临床医学院)
    2250014 济南,山东中医药大学附属医院内分泌科
    3250014 济南,山东第一医科大学第一附属医院肛肠外科
  • 收稿日期:2024-12-16 出版日期:2025-08-25
  • 通信作者: 武国亮
  • 基金资助:
    国家自然基金青年项目(No. 82205129); 山东省自然基金青年项目(No. ZR2022QH161); 济南市科技局临床医学科技创新计划资助项目(No. 202019104); 山东省自然基金项目(No. ZR2021MH137); 山东省中医药科技项目面上项目(No. 2020M048)

The effect of sacral nerve stimulation on 5-HT4R expression in the colon of mice with slow transit constipation

Xiaoyao Chen1, Li Li2, Bing Sun3, Tao Li3, Meng Cui3, Guoliang Wu3,()   

  1. 1The First Affiliated Hospital of Shandong First Medical University, Ji’nan 250014, China
    2Department of Endocrinology, the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji’nan 250014, China
    3Department of Anorectal Surgery, the First Affiliated Hospital of Shandong First Medical University, Ji’nan 250014, China
  • Received:2024-12-16 Published:2025-08-25
  • Corresponding author: Guoliang Wu
引用本文:

陈晓瑶, 李丽, 孙冰, 李涛, 崔萌, 武国亮. 骶神经电刺激对慢传输型便秘小鼠结肠5-HT4R表达的影响[J/OL]. 中华结直肠疾病电子杂志, 2025, 14(04): 345-352.

Xiaoyao Chen, Li Li, Bing Sun, Tao Li, Meng Cui, Guoliang Wu. The effect of sacral nerve stimulation on 5-HT4R expression in the colon of mice with slow transit constipation[J/OL]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2025, 14(04): 345-352.

目的

通过观察骶神经电刺激(SNS)对慢传输型便秘(STC)小鼠结肠组织中5-羟色胺4受体(5-HT4R)表达的影响,探讨SNS治疗STC的作用机制。

方法

将30只昆明小鼠随机分为正常组和造模组,正常组10只,造模组20只。造模组采用复方地芬诺酯混悬液灌胃,正常组正常喂养。STC小鼠模型成功后,将造模组随即均分为SNS组和模型组。SNS组小鼠采用骶神经电刺激治疗;正常组与模型组于骶3神经孔对应的皮肤位置每日浅刺一次,各组均持续治疗2周。治疗结束后,检测各组小鼠粪便含水率、肠道推进率、结肠组织中5-HT4R蛋白的表达、5-HT4R mRNA的表达量、c-kit免疫组化表达等。

结果

与正常组相比,模型组小鼠粪便含水率(t=22.43,P<0.05)和肠道推进率明显降低(t=12.67,P<0.05),结肠组织中5-HT4R的蛋白表达量(t=5.96,P<0.05)、5-HT4R mRNA的表达量(t=9.92,P<0.05)、结肠组织c-kit蛋白免疫组化的表达量(t=5.44,P<0.05)明显降低。与模型组相比,SNS组小鼠粪便含水率(t=19.36,P<0.05)和肠道推进率(t=7.47,P<0.05)明显升高,结肠组织中5-HT4R的蛋白(t=4.76,P<0.05)及5-HT4R mRNA的表达量(t=13.74,P<0.05)、c-kit蛋白免疫组化的表达量明显升高(t=5.39,P<0.05)。

结论

SNS能改善STC小鼠的便秘症状,可能与上调小鼠结肠组织中5-HT4R和c-kit的表达、促进结肠Cajal细胞的增殖及细胞功能的提升,改善肠动力有关。

Objective

To explore the mechanism of action of sacral nerve stimulation (SNS) in the treatment of slow transit constipation (STC) by observing its effect on the expression of 5-hydroxytryptamine 4 receptor (5-HT4R) in the colonic tissue of STC mice.

Methods

Thirty Kunming mice were randomly divided into normal and modeling groups, with 10 mice in the normal group and 20 mice in the modeling group. The modeling group was gavaged with compound difenocoumarol suspension, and the normal group was fed normally. After the success of the STC mouse model, the modeling group was then divided into the SNS group and the model group. The SNS group received sacral nerve stimulation therapy; the normal group and the model group were subjected to daily acupuncture at the skin site corresponding to the S3 nerve foramen, with a 2-week treatment duration for all groups. After treatment, the fecal moisture content, intestinal propulsion rate, expression of 5-HT4R protein, 5-HT4R mRNA expression levels, and c-kit immunohistochemistry in the colon were measured in each group.

Results

Compared with the normal group, the model group showed significantly reduced fecal moisture content (t=22.43, P<0.05) and intestinal propulsion rate (t=12.67, P<0.05), as well as significantly decreased expression of 5-HT4R protein (t=5.96, P<0.05), 5-HT4R mRNA (t=9.92, P<0.05), and c-kit protein immunohistochemistry in the colonic tissue (t=5.44, P<0.05). Compared with the model group, the SNS group exhibited significantly increased fecal moisture content (t=19.36, P<0.05) and intestinal propulsion rate (t=7.47, P<0.05), along with significantly increased expression of 5-HT4R protein (t=4.76, P<0.05), 5-HT4R mRNA (t=13.74, P<0.05), and c-kit protein immunohistochemistry in the colonic tissue (t=5.39, P<0.05).

Conclusion

Sacral nerve stimulation may alleviate constipation symptoms in STC mice, potentially associated with the upregulation of 5-HT4R and c-kit expression in colonic tissues, which may promote the proliferation of interstitial cells of Cajal, enhance their cellular function, and ultimately improve intestinal motility.

图1 骶神经电刺激治疗过程
图2 各组小鼠造模前(2A)、造模后(2B)、治疗后24 h(2C)粪便粒数对比(粒)
图3 各组小鼠造模前(3A)、造模后(3B)、治疗后(3C)粪便含水率对比
图4 各组小鼠肠道推进率对比
图5 各组小鼠结肠组织中5-HT4R mRNA相对表达量
图6 各组小鼠结肠组织中5-HT4R蛋白的相对表达。6A:Western blot图;6B:相对表达量柱状图
图7 各组小鼠结肠组织中c-kit蛋白免疫组化表达(×400)。7A:正常组;7B:SNS组;7C:模型组;7D:c-kit阳性面积占比
[1]
Vlismas LJ, Wu W, Ho V. Idiopathic slow transit constipation: pathophysiology, diagnosis, and management[J]. Medicina (Kaunas), 2024, 60(1): 108.
[2]
Maeda Y, O’Connell PR, Lehur PA, et al. Sacral nerve stimulation for faecal incontinence and constipation: a European consensus statement[J]. Colorectal Dis, 2015, 17(4): 74-87.
[3]
陈璐,王志民,张振, 等. 骶神经电刺激治疗慢传输型便秘的临床研究[J]. 中国肛肠病杂志, 2017, 37(8): 56-58.
[4]
武国亮,李丽. 骶神经电刺激联合TML液封闭治疗慢传输型便秘的临床研究[J]. 中国现代普通外科进展, 2021, 24(8): 646-647, 650.
[5]
Black CJ, Ford AC. Chronic idiopathic constipation in adults: epidemiology, pathophysiology, diagnosis and clinical management[J]. Med J Aust, 2018, 209(2): 86-91.
[6]
Shin JE, Park KS, Nam K. Chronic functional constipation[J]. Korean J Gastroenterol, 2019, 73(2): 92-98.
[7]
许燕城,刘启鸿,柯晓. 慢传输型便秘动物模型的研究进展[J]. 医学综述, 2022, 28(8): 1561-1567.
[8]
Wang XM, Lv LX, Qin YS, et al. Ji-Chuan decoction ameliorates slow transit constipation via regulation of intestinal glial cell apoptosis[J]. World J Gastroenterol, 2022, 28(34): 5007-5022.
[9]
于金娜,刘志顺,马晓晶, 等. 大鼠"次髎"穴的定位和解剖结构[J]. 针刺研究, 2007, 32(5): 334.
[10]
胡俊威,金珠,李旭, 等. 小鼠"次髎"穴的取穴方法研究[J]. 上海中医药大学学报, 2024, 38(4): 55-61.
[11]
中国医师协会肛肠医师分会,中国医师协会肛肠医师分会功能性疾病专业委员会. 慢传输型便秘诊断评估与外科处理中国专家共识(2023版)[J]. 中华胃肠外科杂志, 2023, 26(12): 1112-1121.
[12]
朱国栋,朱安龙. 慢传输型便秘病因机制研究进展[J]. 医学综述, 2020, 26(23): 4623-4628.
[13]
Trinidad S, Jensen A, Holder M, et al. Sacral nerve stimulation in children with medically refractory fecal incontinence or severe constipation[J]. J Pediatr Surg, 2023, 58(8): 1594-1599.
[14]
Yu Z, Zikela L, Wang D, et al. Effects and mechanisms of sciadonic acid on colonic transit function through regulating 5-HT4/cAMP/PKA/AQP4 signaling pathway in STC model mice[J]. J Nutr Biochem, 2024, 131: 109676.
[15]
Mawe GM, Hurd M, Hennig GW, et al. Epithelial 5-HT4 receptors as a target for treating constipation and intestinal inflammation[J]. Adv Exp Med Biol, 2022, 1383: 329-334.
[16]
Gershon MD, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders[J]. Gastroenterology, 2007, 132(1): 397-414.
[17]
Jin X, Guan YT, Bai H, et al. Effects of sEA on slow transit constipation through the microbiota-gut-brain axis in rats[J]. Evid Based Complement Alternat Med, 2020, 2020: 8828846.
[18]
Galligan JJ. Colonic 5-HT4 receptors are targets for novel prokinetic drugs[J]. Neurogastroenterol Motil, 2021, 33(4): e14125.
[19]
Chang L, Chey WD, Imdad A, et al. American gastroenterological association-American college of gastroenterology clinical practice guideline: pharmacological management of chronic idiopathic constipation[J]. Gastroenterology, 2023, 164(7): 1086-1106.
[20]
Huizinga JD, Hussain A, Chen JH. Interstitial cells of Cajal and human colon motility in health and disease[J]. Am J Physiol Gastrointest Liver Physiol, 2021, 321(5): G552-G575.
[21]
林强,张静瑜,秦小金, 等. Cajal间质细胞在慢传输型便秘中的作用及番泻苷A的治疗作用[J]. 山西医科大学学报, 2020, 51(6): 552-559.
[1] 余昌佳, 张怡婷, 张高乐, 李晨光. 慢性便秘肠道菌群与植物源性多糖的研究进展[J/OL]. 中华结直肠疾病电子杂志, 2025, 14(02): 166-173.
[2] 刘昀坤, 孟彩祥, 王乐, 徐越, 叶晨, 李龙, 李宁, 陈启仪. 肠道菌群与慢传输型便秘机制相关研究进展[J/OL]. 中华结直肠疾病电子杂志, 2025, 14(02): 161-165.
[3] 邓玮, 周筛兰, 杨波, 林志亮. 肠道菌群移植治疗便秘患者出院准备度现状及影响因素分析[J/OL]. 中华结直肠疾病电子杂志, 2025, 14(02): 148-154.
[4] 王玲, 樊文彬, 倪嘉淳, 蔡增进. 功能性便秘与焦虑抑郁共病的研究进展[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(05): 411-416.
[5] 王索, 张晓进, 许锋, 王俊, 侍新宇, 孙金兵, 何宋兵. 一例无腹部辅助切口经阴道取出标本的腹腔镜结肠次全切除手术治疗慢传输型便秘的病例报道(附视频)[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(01): 83-88.
[6] 何吉鑫, 杨燕妮, 王继伟, 李建国, 谢铭. 肠道菌群及肠道代谢产物参与慢性便秘发生机制的研究进展[J/OL]. 中华结直肠疾病电子杂志, 2023, 12(06): 495-499.
[7] 李泳龙, 胡经略, 杨振邦, 王天宇, 程鑫群, 吴东蔚, 李承思, 蔚佳昊, 郭海川, 朱燕宾, 张英泽. 物理通便器在老年骨科患者中临床应用的初步研究[J/OL]. 中华老年骨科与康复电子杂志, 2024, 10(02): 65-69.
[8] 贺生霞, 杨凯娜, 李璞. 参苓白术散联合双歧杆菌三联活菌片治疗小儿脾虚型功能性便秘的疗效[J/OL]. 中华消化病与影像杂志(电子版), 2025, 15(01): 73-77.
[9] 李娇娇, 回雪, 杨美荣, 周红军. 穴位电刺激联合中药脐部热熨辅助治疗脑卒中后便秘患者的疗效研究[J/OL]. 中华消化病与影像杂志(电子版), 2025, 15(01): 69-72.
[10] 赵小民, 杨军, 田巍巍. 枳术颗粒联合利那洛肽治疗便秘型肠易激综合征的临床研究[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(05): 465-469.
[11] 陈华, 张欣颖, 潘婕, 周平达, 韩千禧, 杨倩, 朱文涛. 芪蓉润肠口服液系统评价研究[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(03): 263-267.
[12] 韩晓雯, 郗医书, 郭娅, 陈艳珺. 骶神经刺激配合凯格尔运动对产后盆底功能障碍所致便秘患者的临床疗效[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(03): 235-238.
[13] 黄涔, 朱跃坤. 慢传输型便秘分子机制研究及临床应用现状[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(01): 82-89.
[14] 崔国策, 焦霞, 贝绍生, 李华山. 烟草烟雾暴露与成年人便秘风险的关联研究[J/OL]. 中华临床医师杂志(电子版), 2024, 18(12): 1132-1138.
[15] 郑秀丽, 倪敏. 功能性便秘患者的直肠肛门抑制反射特征分析100例[J/OL]. 中华临床医师杂志(电子版), 2023, 17(08): 870-875.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?