中国全科医学 ›› 2023, Vol. 26 ›› Issue (05): 569-575.DOI: 10.12114/j.issn.1007-9572.2022.0510

• 论著 • 上一篇    下一篇

痛泻要方拆方对腹泻型肠易激综合征大鼠脑肠肽的影响研究

王科凯1, 杨焱麟2, 周彦妮1, 肖瑾1, 谢欣1, 吴芹萍1, 陈敏3,*()   

  1. 1.610072 四川省成都市,成都中医药大学
    2.643000 四川省自贡市第五人民医院
    3.610075 四川省成都市,成都中医药大学附属医院
  • 收稿日期:2022-05-29 修回日期:2022-09-01 出版日期:2023-02-15 发布日期:2022-09-22
  • 通讯作者: 陈敏

  • 作者贡献:王科凯、谢欣负责论文起草,并进行结果的分析与解释;王科凯、杨焱麟、周彦妮负责动物模型的制备、实验指标的检测;王科凯、吴芹萍进行数据收集、整理;肖瑾、谢欣进行统计分析、绘制图表;陈敏提出研究的构思与设计,负责研究的实施推进与可行性分析,负责最终版本修订,对论文负责。
  • 基金资助:
    国家自然科学基金面上项目(81774321); 国家重点研发项目"中医药现代化研究"重点专项(2019YFC1709004)

Efficacies of Tong-Xie-Yao-Fang Disassembled Recipes on Brain-gut Peptideina Rat Model of Diarrhea-predominant Irritable Bowel Syndrome

WANG Kekai1, YANG Yanlin2, ZHOU Yanni1, XIAO Jin1, XIE Xin1, WU Qinping1, CHEN Min3,*()   

  1. 1. Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
    2. Zigong Fifth People's Hospital, Zigong 643000, China
    3. Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
  • Received:2022-05-29 Revised:2022-09-01 Published:2023-02-15 Online:2022-09-22
  • Contact: CHEN Min

摘要: 背景 肠易激综合征(IBS)是临床常见的肠道疾病,使用痛泻要方治疗确有疗效,但分析方剂中主要显效药物的相关研究较少。 目的 观察痛泻要方拆方对腹泻型肠易激综合征(IBS-D)大鼠结肠、海马体组织脑源性神经营养因子(BDNF)、P物质(SP)表达的影响。 方法 于2020年7月选取6周龄SPF级雄性Wistar大鼠共32只,采用抽签法随机分为空白组、模型组、白芍防风组(B-F组)和陈皮白术组(C-B组),每组8只。除空白组外,其余各组均使用结直肠扩张+慢性束缚应激法建立内脏敏感型IBS-D大鼠模型。造模后B-F组采用白芍防风中药浸膏(4 ml/kg)灌胃治疗,C-B组采用陈皮白术中药浸膏(4 ml/kg)灌胃治疗,空白组和模型组采用蒸馏水灌胃,治疗周期为14 d。比较造模后、治疗后四组大鼠体质量及增长情况、布里斯托大便分类法评分、不同压力梯度下腹部撤退反射(AWR)、结肠及海马体组织中BDNF和SP表达水平的差异。 结果 建立IBS-D模型大鼠成功,所有大鼠存活。B-F组、C-B组大鼠造模后体质量增长量小于空白组,治疗后体质量增长量大于模型组(P<0.05)。模型组大鼠治疗后布里斯托大便分类法评分高于空白组(P<0.05);B-F组和C-B组大鼠治疗后布里斯托大便分类法评分低于模型组(P<0.05)。治疗后在气囊压力为60 mm Hg时:模型组大鼠AWR评分均高于空白组(P<0.05)。治疗后在气囊压力为60、80 mm Hg时:B-F组大鼠AWR评分低于模型组、C-B组(P<0.05)。模型组、C-B组大鼠治疗后结肠组织BDNF、SP表达水平高于空白组(P<0.05);B-F组大鼠治疗后结肠组织BDNF、SP表达水平低于模型组和C-B组(P<0.05)。模型组大鼠治疗后海马组织BDNF表达水平低于空白组(P<0.05);模型组、C-B组大鼠治疗后海马组织SP表达水平高于空白组(P<0.05);B-F组大鼠治疗后海马组织BDNF表达水平高于模型组,SP表达水平低于模型组(P<0.05)。 结论 痛泻要方中白芍防风药对、陈皮白术药对均能明显增加IBS-D大鼠体质量、改善腹泻情况。相较于陈皮白术药对,白芍防风药对可明显缓解IBS-D大鼠肠道高敏感,更好地下调海马组织SP和结肠组织BDNF、SP的表达,上调海马组织BDNF的表达,调节相关脑肠肽的平衡。

关键词: 肠易激综合征, 腹泻型肠易激综合征, 痛泻要方, 中草药, 内脏高敏, 脑源性神经营养因子, P物质

Abstract:

Background

Tong-Xie-Yao-Fang decoction has proven to be effective for irritable bowel syndrome (IBS) , a common intestinal disease. However, there are few studies on the main active ingredients in the decoction.

Objective

To examine the effects of Tong-Xie-Yao-Fang disassembled recipes on the expression levels of brain-derived neurotrophic factor (BDNF) and substance P (SP) in colon and hippocampus in a rat model of diarrhea-predominant irritable bowel syndrome (IBS-D) .

Methods

On July 2020, a total of 32 6-week-old SPF male Wistar rats were selected and randomized into blank group, model group, baishao-fangfeng group (B-F group) and chenpi-baizhu group (C-B group) , with 8 rats in each. Except for the blank group, the other three groups were used to establish visceral sensitive IBS-D rat model by use of colorectal dilatation + chronic restraint stress. At the end of successful model creation, the B-F group received the solution extracted from both baishao and fangfeng using gavage administration (4 ml/kg) , C-B group received the solution extracted from both chenpi and baizhu using gavage administration (4 ml/kg) , and the other two groups received gavage administration of distilled water. This treatment period was 14 days for all groups. The weight and growth status of weight, stool classification according to the Bristol Stool Scale (BSS) , abdominal withdrawal reflex (AWR) under different pressure gradients, BDNF and SP expression levels in colon and hippocampus were compared between the four groups at the end of modeling and subsequent treatment.

Results

All rats survived when the IBS-D model was successfully created. Blank group had bigger average growth of weight after modeling period than both B-F and C-B groups (P<0.05) . B-F and C-B groups had bigger average growth of weight after the treatment than model group (P<0.05) . Compared with model group, blank group had lower average score of BSS after treatment, and so did both B-F and C-B groups (P<0.05) . After the treatment, the AWR score under 60 mm Hg of cuff pressure in the model group was higher than that in the blank group (P<0.05) , and under both 60 mm Hg or 80 mm Hg of cuff pressure, the AWR score in the B-F group was lower than that in model group or C-B group (P<0.05) . Model group had higher average post-treatment expression levels of BDNF and SP in colon tissue than both blank group and B-F group, and so did C-B group (P<0.05) . Model group had lower average post-treatment expression level of BDNF in hippocampus than blank group (P<0.05) . B-F group had higher average post-treatment expression level of BDNF in hippocampus than both model group (P<0.05) . Model group had higher average post-treatment expression level of SP in hippocampus than both blank group and B-F group (P<0.05) . C-B group had higher expression level of SP in hippocampus than blank group (P<0.05) .

Conclusion

Both Tong-Xie-Yao-Fang disassembled recipes could significantly improve weight and diarrhea in rat model of IBS-D. Compared with chenpi and baizhu, baishao and fangfeng could better alleviate intestinal hypersensitivity, and down-regulate SP expression level in colon and hippocampus, and BDNF expression level in colon, up-regulate the BDNF expression level in colon, and regulate the balance of related brain-gut peptides.

Key words: Irritable bowel syndrome, Diarrheatype irritable bowel syndrome, Tong-Xie-Yao-Fang, Drugs, Chinese herbal, Visceral hypersensitivity, Brain-derived neurotrophic factor, Substance P