固肠胶囊治疗腹泻型IBS模型大鼠效应及长链非编码RNA机制研究

Effects of Guchang capsules treatment and long chain and non coding RNA research on diarrhea-predominant of IBS in rat model

关键词:  固肠胶囊  腹泻型肠易激综合征  TNF-α  IL-6  lncRNA

Key words:  Guchang capsule  diarrhea-predominant irritable bowel syndrome  Tnf-α  IL-6  lncRNA

摘要:

[目的] 阐释固肠胶囊治疗腹泻型肠易激综合征（IBS）模型大鼠效应及长链非编码RNA机制研究。[方法] 建立腹泻型（D-IBS）大鼠模型，随机分为正常组、模型组、固肠胶囊低剂量组、固肠胶囊中剂量组、固肠胶囊高剂量组及匹维溴铵组，正常组和模型组大鼠以生理盐水灌胃，固肠胶囊低剂量、固肠胶囊中剂量组、固肠胶囊高剂量组以同浓度、不同剂量的固肠胶囊溶液，匹维溴铵组以治疗剂量的匹维溴铵灌胃；观察各组的病理结果和炎症因子肿瘤坏死因子-α（TNF-α）和白介素-6（IL-6）及筛选出的特异表达lncRNA水平变化。[结果] 1）各组大鼠结肠均未见明显异常病理。2）固肠胶囊中剂量组和固肠胶囊高剂量组可使结肠组织TNF-α和IL-6水平明显下降，趋于正常，与固肠胶囊低剂量组相比差异有统计学意义（P<0.05）。3）筛选出2条上调特异表达lncRNAs （lncRNA ENSMUST00000153774和AK139722）、2条下调特异表达lncRNAs （lncRNA ENSMUST00000145087和NR_030708），在正常组与模型组样本中，lncRNA ENSMUST00000153774和AK139722在模型组呈相对高表达（P<0.05），模型组 > 固肠胶囊低剂量组 > 固肠胶囊中剂量组 > 固肠胶囊高剂量组 > 匹维溴铵组；lncRNA ENSMUST00000145087和NR_030708在正常组呈相对高表达（P<0.05），正常组 > 固肠胶囊低剂量组 > 固肠胶囊中剂量组>固肠胶囊高剂量组 > 匹维溴铵组，且除固肠胶囊高剂量组与匹维溴铵组比较无统计学差异，其他两组间比较均有统计学差异。[结论] 炎性因子指标TNF-α、IL-6和lncRNA与D-IBS的发生发展有着密切的相关性，固肠胶囊能通过调节TNF-α、IL-6和特异表达lncRNAs的表达水平治疗D-IBS，为后续研究奠定了理论和实验基础，为中药治疗本病提供了可靠的新理论和新靶点。

Abstract:

[Objective] To investigate the effect of Guchang treatment and long chain and non coding RNA research on diarrhea-predominant IBS (D-IBS) in rat model.[Methods] Establish the rat model of diarrhea type irritable bowel syndrome. The rats were randomly assigned to normal group, model group, low dose of Guchang group, middle dose of Guchang group, high dose of Guchang group and pinaverium bromide group. The rat models of normal group and model group, received normal saline, The low dose, middle dose and high dose of Guchang groups were given the solution of Guchang with same concentration and different doses, the last pinaverium bromide group treated with Pinaverium ammonium dose. Observed the pathological results,the changes of TNF-α and IL-6 and the lncRNA in colon tissuein each group. [Results] 1)There was no obvious abnormal pathology in colonic of rats in each group. 2)The levels of TNF-α and IL-6 in colon tissue were significantly decreased and tended to be normal in middle dose and high dose of Guchang groups; the difference is proved to have statistical significance (P<0.05) Compared with pinaverium bromide group. 3)Randomly chose 4 (2 up-regulated, 2 down-regulated) differential expression lncRNAs. The results showed that in samples of normal group and model group, the 2 up-regulated lncRNAs showed relatively high expression in the model group (P<0.05, n=30), model group > low dose of Guchang > middle dose group of Guchang > high dose group of Guchang > pinaverium bromide group, in addition that the high dose group had no significant difference with pinaverium bromide group. The 2 down-regulated lncRNAs showed relatively high expression in normal group (P<0.05), normal group > low dose of Guchang > middle dose group of Guchang > high dose group of Guchang > pinaverium bromide group. There was a significant difference between the other two groups, in addition that the high dose group had no significant difference with pinaverium bromide group.[Conclusion] The occurrence and development of D-IBS has a close relationship with Inflammatory factor TNF-α, IL-6 and lncRNA. Guchang can treat D-IBS by regulating TNF-α, IL-6 and the expression level of specific lncRNA. It lays a theoretical and experimental foundation for the following research, and provides a reliable new theory and new target of Chinese medicine to treat this disease.