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地榆皂苷Ⅰ对脓毒症大鼠急性肺损伤的保护作用及机制研究
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| 篇名： | 地榆皂苷Ⅰ对脓毒症大鼠急性肺损伤的保护作用及机制研究 |
| TITLE： | Study on protective effects and mechanism of ziyuglycoside Ⅰ on acute lung injury in sepsis rats |
| 摘要： | 目的 基于网络药理学方法探讨地榆皂苷Ⅰ对脓毒症大鼠急性肺损伤的保护作用及机制，并通过实验进行验证。方法使用网络药理学方法预测地榆皂苷Ⅰ治疗脓毒症急性肺损伤的潜在靶点。采用盲肠结扎穿孔术复制大鼠脓毒症模型进行实验验证。将192只SD大鼠按随机数字表法分为假手术组（Sham组）、脓毒症组（Sep组）、常规治疗组（CT组）和地榆皂苷Ⅰ治疗组（ZgⅠ组）。Sham组、Sep组给予无菌生理盐水，CT组和ZgⅠ组大鼠给予相应剂量的林格氏液和地榆皂苷Ⅰ。观察各组大鼠动脉血气、血清炎症因子、肺湿/干质量比、肺组织病理变化、肺血管通透性、肺静脉紧密连接蛋白1（ZO-1）和血管内皮钙黏蛋白（VE-cadherin）蛋白表达、72h存活情况。结果网络药理学结果显示，地榆皂苷Ⅰ治疗脓毒症的潜在靶点有47个，基因本体功能富集分析和京都基因与基因组百科全书通路富集分析结果显示，其机制可能与活性氧族代谢正向调控（positiveregulationofreactiveoxygenspeciesmetabolicprocess）、损伤修复（wouldhealing）、内皮细胞增殖调控（regulationtoendothelialcellproliferation）、细胞激活（cellactivation）、血管发生（bloodvesseldevelopment）、氧化应激反应（responsetooxidativestress）等生物学过程和细胞凋亡（apoptosis）、紧密连接（tightjunction）、缺氧诱导因子1信号通路（HIF-1αsignalingpathway）等信号通路有关。实验验证结果显示，与Sham组比较，Sep组大鼠动脉氢离子浓度指数、动脉血氧分压水平显著降低（P＜0.05），二氧化碳分压水平、血清肿瘤坏死因子α、白细胞介素6水平显著升高（P＜0.05）；肺湿/干质量比显著升高（P＜0.05）；肺静脉ZO-1、VE-cadherin蛋白表达水平显著降低（P＜0.05）；72h存活率明显降低，存活时间显著缩短（P＜0.05）；肺组织病理观察结果显示，大鼠肺泡出现大范围破裂，肺泡壁增厚并伴有水肿，有明显炎性细胞浸润；肺血管通透性观察结果显示，大鼠肺表面颜色暗淡，有大量伊文思蓝渗出，左下肺呈明显深蓝色。与Sep组比较，CT组和ZgⅠ组以上指标水平大部分显著逆转（P＜0.05），肺组织病理和肺血管通透性均明显改善，其中ZgⅠ组恢复程度大于CT组，接近Sham组结果。结论地榆皂苷Ⅰ可显著减轻脓毒症大鼠炎症反应及急性肺损伤，其机制与血管功能和紧密连接信号通路有关。 |
| ABSTRACT： | OBJECTIVE To investigate the protective effects and mechanism of ziyuglycoside Ⅰ on acute lung injury in sepsis rats based on network pharmacology， and conduct experimental verification. METHODS The network pharmacology was used to predict the potential target of ziyuglycoside Ⅰ in the treatment of acute lung injury following sepsis. The rat model of sepsis was reproduced by cecum ligation and puncture for experimental verification. Totally 192 SD rats were randomly divided into the sham operation group （Sham group）， sepsis group （Sep group）， conventional therapy group （CT group） and ziyuglycoside Ⅰ group （Zg Ⅰ group）， respectively. Sham group and Sep group were given sterile normal saline， and CT group and ZgⅠ group were given relevant volume of Ringer’s solution and ziyuglycoside Ⅰ. The arterial blood gas， serum inflammatory factors， lung wet/dry mass ratio， pathological changes of lung tissue， pulmonary vascular permeability， the expressions of pulmonary vein tight junction protein 1 （ZO-1） and vascular endothelial cadherin （VE-cadherin） protein and 72-hour survival were observed in each group. RESULTS Results of network pharmacology showed that there were 47 potential targets of ziyuglycoside Ⅰ in the treatment of sepsis. The results of gene ontology function enrichment analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that the mechanism could 598486924@qq.com be correlated with biological processes such as positive regulation of reactive oxygen species metabolism， wound healing， regulation of endothelial cell proliferation， cell activation， blood vessel development， response to oxidative stress， etc.， and with signaling pathway such as apoptosis， tight junction， HIF-1 signaling pathway， etc. The results of experimental verification showed that compared with Sham group， pH value and the level of partial arterial oxygen pressure were decreased significantly in Sep group （P＜0.05）， while the level of partial pressure of carbon dioxide， serum levels of tumor necrosis factor α， interleukin 6 were increased significantly （P＜0.05）； the ratio of lung wet/dry mass was increased significantly （P＜0.05）； the protein expressions of ZO-1 and VE-cadherin were decreased significantly （P＜0.05）； 72 h survival rate decreased，the survival time was significantly shortened （P＜0.05）； the results of pathological observation of lung tissue showed that the rats’ alveoli were extensively ruptured， the alveolar wall was thickened and accompanied with edema， and there was obvious inflammatory cell infiltration； the results of pulmonary vascular permeability observation showed that the lung surface of rats was dark， with a large amount of Evans blue exudation， and the left lower lung was obviously dark blue. Compared with Sep group， the levels of above indexes almost were reversed significantly in CT group and ZgⅠ group （P＜0.05）； the lung histopathology and pulmonary vascular permeability were significantly improved， and the recovery degree of ZgⅠ group was greater than that of CT group， which was close to the results of Sham group. CONCLUSIONS Ziyuglycoside Ⅰ can significantly reduce inflammatory reaction and acute lung injury in septic rats， which is related to vascular function and tight junction signal pathway. |
| 期刊： | 2023年第34卷第05期 |
| 作者： | 包代琴；刘奕言；张紫森；佘汉；谭磊；李涛；毛庆祥；刘良明 |
| AUTHORS： | BAO Daiqin，LIU Yiyan，ZHANG Zisen，SHE Han，TAN Lei，LI Tao，MAO Qingxiang，LIU Liangming |
| 关键字： | 地榆皂苷Ⅰ；脓毒症；急性肺损伤；网络药理学；紧密连接；黏附连接 |
| KEYWORDS： | ziyuglycoside Ⅰ； sepsis； acute lung injury； network pharmacology； tight junction； adherent junction |
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