南方医科大学学报

南方医科大学学报 ›› 2024, Vol. 44 ›› Issue (4): 720-726.doi: 10.12122/j.issn.1673-4254.2024.04.14

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决明子脐贴对慢传输型便秘大鼠的治疗作用及谱效关系

黄 莉，程索婷，刘 竹，邹纯才，鄢海燕   

  1. 皖南医学院药学院，安徽 芜湖 241002
  • 发布日期:2024-04-29

Transdermal patches containing Cassia seed extract applied at the navel for slow transit constipation in rats: therapeutic effect and analysis of the spectrum-effect relationship

HUANG Li, CHENG Suoting, LIU Zhu, ZOU Chuncai, YAN Haiyan   

  1. School of Pharmacy, Wannan Medical College, Wuhu 241002, China
  • Published:2024-04-29

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摘要： 目的 研究决明子脐贴对慢传输型便秘（STC）大鼠的治疗作用及谱效关系。方法 将大鼠随机分为空白对照组、模型组、便秘贴阳性对照组和决明子脐贴低、中、高剂量组，6只/组。以复方地芬诺酯混悬液连续灌胃14 d建立STC大鼠模型。造模成功后，将决明子脐贴按低、中、高剂量（41.75、125.25、375.75 mg/kg）固定于大鼠腹部神阙穴处，连续给药 14 d，以便秘贴（13.33 mg/kg）为阳性对照组，空白对照组与模型组给予等体积的纯水灌胃。观察大鼠的一般情况，计算大鼠粪便含水率、肠道推进率，HE染色观察大鼠结肠病理改变，测定大鼠血清中NO、NOS水平以及结肠组织中总蛋白含量、NO、NOS、AChE水平。建立决明子脐贴的HPLC指纹图谱，采用均值法和灰色关联度分析法研究决明子脐贴共有峰与对STC大鼠治疗作用的谱效关系。结果 决明子脐贴能提高大鼠粪便含水率、肠道推进率，HE染色观察未发现结肠组织有病理学改变。与空白对照组比较，模型组大鼠血清与结肠中的NO、NOS水平上升（P<0.05，P<0.01），AChE水平下降（P<0.05，P<0.01）；与模型组比较，各给药组大鼠血清与结肠中NO、NOS水平下降（P<0.05，P<0.01），AChE水平上升（P<0.05，P<0.01）。6批决明子脐贴共确认28个共有峰，根据谱效关系得到的关联度与关联序结果显示，决明子脐贴中各成分对STC大鼠的治疗作用贡献度不同，其中橙黄决明素的贡献最大。结论 决明子脐贴通过不同给药剂量的多种活性成分协同发挥对STC大鼠的治疗作用，其中橙黄决明素、大黄酸、黄决明素、决明素、美决明素、大黄素、大黄酚、大黄素甲醚是决明子脐贴治疗STC的主要药效成分群。

关键词: 慢传输型便秘；决明子脐贴；肠道推进率；灰色关联度分析法；谱效关系

Abstract: Objective To explore the therapeutic effect of transdermal patches containing Cassia seed extract applied at the navel on slow transit constipation (STC) in rats and explore the spectrum- effect relationship of the patches. Method In a STC rat model established by gavage of compound diphenoxylate suspension for 14 days, the transdermal patches containing low, medium and high doses of Cassia seed extract (41.75, 125.25, and 375.75 mg/kg, respectively) were applied at the Shenque acupoint on the abdomen for 14 days after modeling, with constipation patches (13.33 mg/kg) as the positive control. After the treatment, fecal water content and intestinal propulsion rate of the rats were calculated, the pathological changes in the colon were observed with HE staining. Serum NO and NOS levels and the total protein content and NO, NOS and AChE expressions in the colon tissue were determined. HPLC fingerprints of the transdermal patches were established, and the spectrum-effect relationship between the common peaks of the patches and its therapeutic effect were analyzed. Results Treatment with the transdermal patches containing Cassia seed extract significantly increased fecal water content and intestinal propulsion rate of the rat models, where no pathological changes in the colon tissue were detected. The treatment also suppressed the elevations of serum and colonic NO and NOS levels and reduction of AChE in STC rats. Twenty-eight common peaks were confirmed in the HPLC fingerprints of 6 batches of Cassia seed extract- containing patches. Analysis of the spectrum- effect relationship showed that autrantio- obtusin had the greatest contribution to the therapeutic effect of the patches in STC rats. Conclusion The Cassia seed extract- containing patches alleviates STC in rats via synergistic actions of multiple active ingredients in the extract, where autrantio-obtusin, rhein, chrysoobtusin, obtusin, obtusifolin, emodin, chrysophanol, and physcion are identified as the main active ingredients.

Key words: slow transit constipation; transdermal patches containing Cassia seed extract; intestinal propulsion rate; grey relation analysis method; spectrum-effect relationship