Pulsatilla Decoction Can Treat the Dampness-Heat Diarrhea Rat Model by Regulating Glycerinphospholipid Metabolism Based Lipidomics Approach
Pulsatilla Decoction Can Treat the Dampness-Heat Diarrhea Rat Model by Regulating Glycerinphospholipid Metabolism Based Lipidomics Approach
复制标题
基于脂质组学方法白头翁汤调节甘油磷脂代谢治疗湿热腹泻大鼠模型
DOI：
10.3389/fphar.2020.00197
复制
发表时间：
2020-03-03
影响因子：
5.6
通讯作者：
Wei Yan-ming
中科院分区：
文献类型：
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作者：
Hua Yong-li;Ma Qi;Wei Yan-ming
腹泻是临床实践中的一个重大医学问题。根据中医理论，不同类型的腹泻应根据不同的医疗状况使用不同的中药配方进行治疗。湿热腹泻（DHD）是一种严重的腹泻疾病，白头翁汤（PD）是一种有效的中药。目的利用非靶向脂质组学方法，探讨PD治疗DHD的作用机制。材料与方法Wistar大鼠随机分为4组：对照组、模型组、PD组和自愈组。PD组每天灌胃PD，剂量为3.76 g/kg。采用高糖高脂饮食、饮食不当、高温高湿环境、饮水及腹腔注射大肠杆菌等复杂因素建立大鼠DHD模型。，模拟了DHD的诱导条件。观察患者的临床症状体征、血常规、血清炎症因子水平及主要脏器组织病理学变化，评价帕金森病的DHD模型及治疗效果。采用结肠脂质组学技术和超高效液相色谱（UHPLC）联用Q - Exactive +质谱分析仪对对照组和模型组进行比较，选择DHD的脂质生物标志物。采用多元统计分析和模式识别方法检测pd治疗大鼠结肠内不同脂质。结果模型大鼠的临床症状和体征符合DHD诊断标准。PD治疗后，DHD大鼠的临床症状和体征得到改善；血常规指标及炎症因子水平趋于正常。与对照组相比，模型组小鼠脂质组学谱明显紊乱。通过多变量统计分析，模型对照组之间共有42例血脂发生显著改变。DHD可能是由与甘油磷脂代谢、花生四烯酸（AA）代谢和鞘脂代谢有关的脂质紊乱引起的。PD治疗后，与模型组相比，疾病的脂质组学特征有恢复的趋势。鉴定出20个脂质分子，部分甘油磷脂和AA水平恢复到接近正常水平。结论甘油磷脂代谢可能在PD治疗湿热腹泻中起重要作用。
Ethnopharmacological Relevance Diarrhea is a major medical problem in clinical practice. According to the theory of traditional Chinese medicine (TCM), different types of diarrhea should be treated with different TCM formulations based on the targeted medical condition. Dampness-heat diarrhea (DHD) is a serious diarrheal disease and Pulsatilla decoction (PD), a TCM, has been found effective against DHD. Objective The aim of this study was to clarify the mechanism of action of PD in DHD using an untargeted lipidomics strategy. Materials and Methods Wistar rats were randomized to four groups, including the control group, model group, PD groups and self-healing group. The PD groups were given a daily intragastric gavage of PD at doses of 3.76 g/kg. The rat model of DHD established by such complex factors as high-sugar and high-fat diet, improper diet, high temperature and humidity environment, drinking and intraperitoneal injection of Escherichia coli., which imitated the inducing conditions of DHD. Then the clinical symptoms and signs, blood routine, serum inflammatory cytokines levels and the histopathological changes of main organs were detected and observed to evaluate DHD model and therapeutic effect of PD. Lipid biomarkers of DHD were selected by comparing the control and model groups with the colon lipidomics technology and an ultra-high performance liquid chromatography (UHPLC) coupled with Q Exactive plus mass analyzer. Multivariate statistical analysis and pattern recognition were employed to examine different lipids within the colon of PD-treated rats. Results The clinical symptoms and signs of the model rats were consistent with the diagnostic criteria of DHD. After treatment with PD, the clinical symptoms and signs of the rats with DHD were improved; the indexes of blood routine and inflammatory cytokines levels tended to be normal. The lipidomics profile of the model group were evidently disordered when compared to the control group. A total of 42 significantly altered lipids between the model-control groups were identified by multivariate statistical analysis. DHD may result from such lipid disorders which are related to glycerophospholipid metabolism, arachidonic acid (AA) metabolism, and sphingolipid metabolism. After PD treatment, the lipidomic profiles of the disorders tended to recover when compared to the model group. Twenty lipid molecules were identified and some glycerophospholipids and AA levels returned close to the normal level. Conclusion Glycerophospholipid metabolism may play an important role in the treatment of dampness-heat induced diarrhea using PD.