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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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郭春风 ,蒋 鑫 ,程汝阳 ,刘树民 ,谢春祥 ,卢 芳 (1.黑龙江中医药大学附属第二医院哈南分院中医内
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科,哈尔滨 150040;2.黑龙江中医药大学中医药研究院,哈尔滨 150040;3.黑龙江蟾宝生物科技发展有限公
司,黑龙江 鹤岗 154100)
中图分类号 R965;R285 文献标志码 A 文章编号 1001-0408(2025)13-1622-07
DOI 10.6039/j.issn.1001-0408.2025.13.12
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,0.32 g/kg凡士林),模型组(Model组,0.32 g/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、0.64 g/kg),马应龙麝香痔疮栓组(Positive组,
0.32 g/kg),每组9只;分别于造模后6、12、24、48、72 h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P450 1B1(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。
关键词 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
Study on mechanism of Chanbao zhichuang suppository in treating hemorrhoids based on network
pharmacology and metabolomics
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GUO Chunfeng ,JIANG Xin ,CHENG Ruyang ,LIU Shumin ,XIE Chunxiang ,LU Fang(1. Dept. of TCM
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Internal Medicine, Hanan Branch of Second Affiliated Hospital of Heilongjiang University of Chinese Medicine,
Harbin 150040, China;2. Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese
Medicine, Harbin 150040, China;3. Heilongjiang Chanbao Biotechnology Development Co., Ltd., Heilongjiang
Hegang 154100, China)
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
Δ 基金项目 黑龙江省中医药管理局第二批省级名中医专家传承
pathways were screened by interaction and enrichment analysis
工作室建设项目
*第一作者 副主任医师,博士。研究方向:中医药在内科疾病中 of differential metabolites and proteins, and the core proteins
的应用。E-mail:15004601905@163.com were experimentally verified. RESULTS Compared with the
# 通信作者 研究员,博士生导师,博士。研究方向:中药药性理论 NC group, the anal tissues of the Model group showed
及药效物质基础。E-mail:lufang_1004@163.com obvious lesions, and the levels of IL-6 and TNF- α in the
· 1622 · China Pharmacy 2025 Vol. 36 No. 13 中国药房 2025年第36卷第13期