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基于网络药理学和代谢组学的蟾宝痔疮栓抗痔疮的机制研究
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| 篇名： | 基于网络药理学和代谢组学的蟾宝痔疮栓抗痔疮的机制研究 |
| TITLE： | Study on mechanism of Chanbao zhichuang suppository in treating hemorrhoids based on network pharmacology and metabolomics |
| 摘要： | 目的 通过网络药理学和代谢组学探讨蟾宝痔疮栓（CBZCS）对痔疮大鼠的改善作用机制。方法利用浸吸巴豆油致肛门肿胀建立大鼠痔疮模型。将SD大鼠分为空白组（NC组，0.32g/kg凡士林），模型组（Model组，0.32g/kg凡士林），CBZCS低、中、高剂量组（分别记为CBZCS-L、CBZCS-M、CBZCS-H组，给药剂量分别为0.16、0.32、0.64g/kg），马应龙麝香痔疮栓组（Positive组，0.32g/kg），每组9只；分别于造模后6、12、24、48、72h进行肛门给药。末次给药后，观察大鼠肛门组织病理变化，检测大鼠血清中白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）水平。通过代谢组学的方法进行差异代谢物分析和通路富集分析，运用网络药理学获得CBZCS治疗痔疮的靶点蛋白，联合差异代谢物和靶点蛋白进行交互和富集分析以筛选核心代谢通路，并对核心蛋白进行实验验证。结果与NC组比较，Model组大鼠肛门组织出现明显病变，血清中IL-6、TNF-α水平显著升高（P＜0.05）；与Model组比较，给药组大鼠肛门组织病理损伤均有不同程度缓解，CBZCS-H组、CBZCS-M组、Positive组大鼠血清中IL-6水平和CBZCS-H组大鼠血清中TNF-α水平均显著降低（P＜0.05）。代谢组学结果显示，从大鼠的肛门组织中共筛选出34个差异代谢物，经CBZCS给药后共有22个出现回调。回调的差异代谢物主要富集于花生四烯酸代谢、组氨酸代谢和甘油磷脂代谢通路。通过网络药理学的方法确定了138个CBZCS抗痔疮的交集基因。差异代谢物和靶点蛋白主要富集于花生四烯酸代谢通路，该通路的调控可能与环氧合酶2（COX-2）、Myc原癌基因蛋白（c-MYC）、细胞色素P4501B1（CYP1B1）、白细胞介素1β（IL-1β）、IL-6的蛋白表达有关。实验验证结果显示，Model组大鼠肛门组织中关键蛋白（COX-2、c-MYC、CYP1B1、IL-1β、IL-6）的表达水平均较NC组显著升高（P＜0.05），CBZCS-H组和Positive组大鼠肛门组织中上述蛋白水平均较Model组显著降低（P＜0.05）。结论CBZCS抗痔疮机制可能是抑制COX-2、c-MYC、CYP1B1蛋白的表达，进而抑制花生四烯酸代谢，减少炎症因子IL-6、IL-1β的释放。 |
| ABSTRACT： | OBJECTIVE To explore the mechanism of improvement effect of Chanbao zhichuang suppository （CBZCS） on hemorrhoids in rats through network pharmacology and metabolomics. METHODS A hemorrhoid model was established by subcutaneous injection of rhododendron oil to induce anal swelling. SD rats were divided into blank group （NC group， 0.32 g/kg vaseline）， model group （Model group， 0.32 g/kg vaseline）， CBZCS low-， medium-， and high-dose groups （CBZCS-L， CBZCS- M， CBZCS-H groups， with dosages of 0.16， 0.32， and 0.64 g/kg respectively）， and Mayinglong musk hemorrhoids suppository group （Positive group， 0.32 g/kg）， with 9 rats in each group. Anal administration was performed at 6， 12， 24， 48， and 72 hours after modeling. After the last administration， the pathological changes of the anal tissues in rats were observed， and the serum levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in rats were detected. Differential metabolite analysis and enrichment analysis were conducted by metabolomics methods， and the target proteins of CBZCS in treating hemorrhoids were obtained by network pharmacology. The core metabolic pathways were screened by interaction and enrichment analysis of differential metabolites and proteins， and the core proteins were experimentally verified. RESULTS Compared with the NC group， the anal tissues of the Model group showed obvious lesions， and the levels of IL-6 and TNF- α in the serum were significantly increased （P＜0.05）； compared with the Model group， the pathological damage of the anal tissues in the treatment groups was alleviated to varying degrees， and serum levels of IL-6 in CBZCS-H group， CBZCS-M group， and Positive group as well as serum levels of TNF-α in CBZCS-H group were significantly reduced （P＜0.05）. The metabolomics results showed that 34 differential metabolites were screened from the anal tissues of rats， and 22 of them showed a return after CBZCS administration. The differential metabolites mainly enriched in arachidonic acid metabolism， histidine metabolism， and glycerophospholipid metabolism. Through the network pharmacology， 138 intersection genes of CBZCS against hemorrhoids were determined. The analysis results showed that differential metabolites and target proteins were mainly enriched in the arachidonic acid metabolism pathway， and the regulation of this pathway might be related to cyclooxygenase-2 （COX-2）， Myc proto-oncogene protein （c-MYC）， cytochrome P450 1B1 （CYP1B1）， interleukin-1β （IL-1β）， and IL-6 protein expression. The experimental verification results showed that the expression levels of key proteins （COX-2， c-MYC， CYP1B1， IL-6， IL-1β） in the anal tissues of the Model group were significantly higher than those in the NC group （P＜0.05）， and the levels of the above proteins in the anal tissues of CBZCS-H group and Positive group were significantly lower than those in the Model group （P＜0.05）. CONCLUSIONS The mechanism of CBZCS in treating hemorrhoids may be to inhibit the expression of COX-2， c-MYC and CYP1B1 proteins， thereby inhibiting arachidonic acid metabolism and reducing the release of inflammatory factors IL-6 and IL-1β. |
| 期刊： | 2025年第36卷第13期 |
| 作者： | 郭春风；蒋鑫；程汝阳；刘树民；谢春祥；卢芳 |
| AUTHORS： | GUO Chunfeng，JIANG Xin，CHENG Ruyang，LIU Shumin，XIE Chunxiang，LU Fang |
| 关键字： | 蟾宝痔疮栓；痔疮；花生四烯酸代谢；环氧合酶2；Myc原癌基因蛋白；细胞色素P450 1B1；炎症反应；代谢组学；网络药理学 |
| KEYWORDS： | Chanbao zhichuang suppository； hemorrhoids； arachidonic acid metabolism； cyclooxygenase-2； Myc proto- |
| 阅读数： | 3 次 |
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