| 引用本文:李甫，陈萌，吉建梅，张晞文，丁俊，黄金鑫，唐睿，蔡淦.从调节Cajal细胞自噬探讨芍药甘草汤改善Oddi括约肌功能障碍的机制[J].世界中医药,2021,(02):. |
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| 从调节Cajal细胞自噬探讨芍药甘草汤改善Oddi括约肌功能障碍的机制 |
| Study on the Mechanism of Shaoyao Gancao Decoction on Improving Sphincter Dysfunction of Oddi by Regulating Autophagy of Interstitial Cells of Cajal |
| 投稿时间：2020-03-17 |
| DOI：10.3969/j.issn.1673-7202.2021.02.025 |
| 中文关键词: 芍药甘草汤 Oddi括约肌功能障碍 Cajal间质细胞 细胞自噬 IRE1/Beclin1通路 |
| English Keywords:Shaoyao Gancao Decoction Oddi Sphincter dysfunction Interstitial cells of Cajal Cell Autophagy IRE1/Beclin1 pathway |
| 基金项目:国家自然科学基金项目(81904017);上海市科委“科技创新行动计划”临床医学领域项目(19401972400);上海市浦东新区卫生和计划生育委员会卫生行业科研专项(PW2018E-03) |
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| 中文摘要: |
| 基于芍药甘草汤具有显著改善Oddi括约肌功能障碍(SOD)患者腹痛的临床疗效和抑制自噬相关蛋白(GPR78、Beclin1)的工作基础,结合Cajal间质细胞(ICC)过度自噬将引起平滑肌收缩紊乱、进一步导致SOD的研究进展,探讨芍药甘草汤调节ICC自噬水平及治疗SOD的分子药理机制。首先,复制豚鼠SOD模型,观察芍药甘草汤对Oddi括约肌压力、ICC自噬水平的影响;其次,吗啡刺激诱导离体SOD模型,观察芍药甘草汤对Oddi括约肌肌条收缩曲线、自噬通路的影响;最后,分离原代ICC、构建IRE1基因沉默或过表达载体、衣霉素刺激ICC建立内质网应激模型,予不同浓度的芍药甘草汤孵育,观察ICC内质网应激水平、自噬信号通路的变化。最终验证“芍药甘草汤抑制IRE1/Beclin1信号通路,减轻ICC内质网应激引起的过度自噬,从而改善SOD平滑肌舒张效应”的科学假说,为推进中医药调节胆道动力学的理论研究夯实基础。 |
| English Summary: |
| Based on the clinical effect of Shaoyao Gancao Decoction on abdominal pain of Sphincter of Oddi dysfunction (SOD) patients and the work basis of inhibiting autophagy related proteins (GPR78,Beclin1), combined with the research progress that Cajal interstitial cells (ICC) over autophagy will cause smooth muscle contraction disorder and further lead to SOD research development, to explore the molecular pharmacological mechanism of Shaoyao Gancao Decoction on regulating the level of ICC autophagy and treating SOD. Firstly, the SOD model of guinea pig was duplicated, and the effects of Shaoyao Gancao Decoction on Oddi sphincter pressure and ICC autophagy level was observed; secondly, morphine stimulation induced SOD model in vitro, and the effects of Shaoyao Gancao Decoction on Oddi sphincter contraction curve and autophagy signal pathway of Oddi was observed; finally, we isolated the primary ICC, constructed the silencing or overexpression vector of IRE1 gene, and stimulated ICC by tunicamycin to establish the endoplasmic reticulum stress model, and incubated with different concentrations of Shaoyao Gancao Decoction to observe the changes of endoplasmic reticulum stress level and autophagy signal pathway in ICC. We verified the scientific hypothesis that Shaoyao Gancao Decoction can inhibit IRE1 / Beclin1 signal pathway, reduce excessive autophagy caused by ICC endoplasmic reticulum stress, so as to improve the relaxation effect of SOD smooth muscle, which will lay a solid foundation for the theoretical research of TCM regulating biliary dynamics. |
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