| 摘要: |
| 目的：基于TLR4/MyD88/NF-κB信号通路研究参苓白术散对腹泻型肠易激综合征（IBS-D）大鼠的干预机制。方法：将48只大鼠随机分为空白组、模型组、匹维溴铵组［20 mg/(kg·d）］、参苓白术散组［SLBZ组，1.44 g/（kg·d）］、TLR4抑制剂组［TAK-242组，1 mg/（kg·d）］、TLR4抑制剂+参苓白术散组（TAK-242+SLBZ组），每组各8只。除空白组外，其余各组均采用4%乙酸构建IBS-D大鼠模型。造模成功后，各给药组给予相应的药物灌胃，连续7 d。观察大鼠一般情况，体质量及粪便Bristol评分，结肠组织病理学变化，血清肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）及白细胞介素-1β（IL-1β）水平，结肠组织闭锁小带蛋白-1（ZO-1）、紧密连接蛋白（Occludin）、Toll样受体4（TLR4）、髓样分化因子88（MyD88）、核转录因子-κB p65（NF-κB p65）蛋白表达水平。结果：成功造模38只。与空白组比较，模型组大鼠体质量下降，粪便Bristol评分升高，HE染色可见炎症细胞浸润，血清TNF-α、IL-6及IL-1β水平升高，结肠组织ZO-1与Occludin蛋白水平降低，TLR4、MyD88、NF-κB p65蛋白水平升高（P＜0.05）。与模型组比较，匹维溴铵组、SLBZ组、TAK-242组、TAK-242+SLBZ组大鼠体质量增加，粪便Bristol评分降低，HE染色炎症细胞浸润减少，血清IL-6、IL-1β及TNF-α水平均显著下降，ZO-1和Occludin蛋白表达水平升高，TLR4、MyD88和NF-κB p65蛋白表达水平下降（均P＜0.05）。与匹维溴铵组、SLBZ组、TAK-242组比较，TAK-242+SLBZ组大鼠结肠组织ZO-1与Occludin蛋白表达水平升高，TLR4、MyD88、NF-κB p65蛋白表达水平下降（均P＜0.05）。结论：参苓白术散可改善IBS-D大鼠腹泻症状，降低血清炎症因子水平，修复肠黏膜，其机制可能是通过调控TLR4 /MyD88 /NF-kB信号通路来达到减轻肠道炎症反应的目的。 |
| 关键词: 腹泻型肠易激综合征 参苓白术散 TLR4/MyD88/NF-κB通路 实验研究 |
| DOI： |
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| Intervention mechanism of Shenling Baizhu powder on rats with diarrhea-predominant irritable bowel syndrome: A study based on the TLR4/MyD88/NF-κB signaling pathway |
| ZHU Wei,ZENG Tingting |
| (The First Affiliated Hospital of Hunan University of Chinese Medicine，Changsha 410007，Hunan，China) |
| Abstract: |
| Objective: To investigate the intervention mechanism of Shenling Baizhu powder on rats with diarrhea-predominant irritable bowel syndrome (IBS-D) based on the TLR4/MyD88/NF-κB signaling pathway.Methods: A total of 48 rats were randomly divided into blank group，model group，pinaverium bromide group (20 mg/kg/day)，Shenling Baizhu powder group (SLBZ group，1.44 g/kg/day)，TLR4 inhibitor group (TAK-242 group，1 mg/kg/day)，and TLR4 inhibitor+Shenling Baizhu powder group (TAK-242+SLBZ group)，with 8 rats in each group.All rats except those in the blank group were given 4% acetic acid to establish a rat model of IBS-D.After successful modeling，each administration group was given the corresponding drug by gavage for 7 consecutive days.The rats were observed in terms of general status，body weight，feces Bristol score，colonic histopathological changes，the serum levels of tumor necrosis factor-α (TNF-α)/interleukin-6 (IL-6)/interleukin-1β (IL-1β)，and the protein expression levels of zonula occluden-1 (ZO-1)，tight junction protein Occludin，TLR4，MyD88，and NF-κB p65 in colon tissue.Results: Successful modeling was observed in 38 rats.Compared with the blank group，the model group had a significant reduction in body weight，a significant increase in feces Bristol score，inflammatory cell infiltration shown by HE staining，significant increases in the serum levels of TNF-α，IL-6，and IL-1β，significant reductions in the protein expression levels of ZO-1 and Occludin in colon tissue，and significant increases in the protein expression levels of TLR4，MyD88，and NF-κB p65 (P＜0.05).Compared with the model group，the pinaverium bromide group，the SLBZ group，the TAK-242 group，and the TAK-242+SLBZ group had a significant increase in body weight，a significant reduction in feces Bristol score，a significant reduction in inflammatory cell infiltration shown by HE staining，significant reductions in the serum levels of IL-6，IL-1β，and TNF-α，significant increases in the protein expression levels of ZO-1 and Occludin，and significant reductions in the protein expression levels of TLR4，MyD88，and NF-κB p65 (all P＜0.05).Compared with the pinaverium bromide group，the SLBZ group，and the TAK-242 group，the TAK-242+SLBZ group significant increases in the protein expression levels of ZO-1 and Occludin in colon tissue and significant reductions in the protein expression levels of TLR4，MyD88，and NF-κB p65 (all P＜0.05).Conclusion: Shenling Baizhu powder can improve the symptoms of diarrhea，reduce the serum levels of inflammatory factors，and repair intestinal mucosa in IBS-D rats，possibly by regulating the TLR4/MyD88/NF-κB signaling pathway and alleviating intestinal inflammatory response. |
| Key words: diarrhea-predominant irritable bowel syndrome Shenling Baizhu powder TLR4/MyD88/NF-κB signaling pathway experimental study |
