Page 42 - 《中国药房》2024年22期

姜黄素对子宫内膜异位症模型大鼠的影响及机制
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秦翠梅 ，刘心怡 ，丁晓兰 ，郭会领 ，陈品英 ，刘 姣 ，程 杰 （1.滨州市中医医院妇科，山东 滨州 256601；
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2.河北省中医院药学部，石家庄 050011；3.河北中医药大学中药药理教研室，石家庄 050200）
中图分类号 R965 文献标志码 A 文章编号 1001-0408（2024）22-2744-06
DOI 10.6039/j.issn.1001-0408.2024.22.07
摘 要 目的 基于Notch1信号通路探讨姜黄素对子宫内膜异位症（EMS）模型大鼠的影响及机制。方法 在动情周期趋于一致
的雌性SD大鼠腹壁上种植自体子宫内膜，构建EMS模型，并将其随机分为模型组，姜黄素低、中、高剂量组（60、120、240 mg/kg）
和Notch1抑制剂DAPT组（7 mg/kg），另设假手术组，每组10只。各组大鼠灌胃或尾静脉注射相应药物，给药4周后，分别通过超
声仪和肉眼观察、测量子宫内膜异位病灶并计算体积；观察病灶组织病理形态；检测大鼠腹腔液中白细胞介素1β（IL-1β）、IL-6和
肿瘤坏死因子α（TNF-α）含量，以及子宫内膜异位病灶中Notch1、基质金属蛋白酶9（MMP-9）和血管内皮生长因子（VEGF）mRNA
和蛋白表达水平。结果 与模型组比较，姜黄素低、中、高剂量组和DAPT组大鼠子宫内膜异位病灶的体积均显著减小（P＜0.05），
柱状上皮萎缩或消失，囊泡消失；腹腔液中 IL-1β、IL-6 和 TNF-α（姜黄素低剂量组除外）水平以及子宫内膜异位病灶中 Notch1、
MMP-9和VEGF mRNA（姜黄素低剂量组MMP-9、VEGF除外）及蛋白（姜黄素低剂量组MMP-9除外）表达水平均显著降低（P＜
0.05），其中姜黄素高剂量组和DAPT组大部分指标优于姜黄素低、中剂量组。结论 姜黄素对EMS具有改善作用，其作用机制可
能与抑制Notch1信号通路、减轻局部炎症反应、抑制异位内膜的侵袭和血管生成有关。
关键词 子宫内膜异位症；姜黄素；Notch1信号通路

Impact and mechanism of curcumin on endometriosis model rats
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QIN Cuimei ，LIU Xinyi ，DING Xiaolan ，GUO Huiling ，CHEN Pinying ，LIU Jiao ，CHENG Jie（1. Dept. of
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Gynecology， Binzhou Hospital of Traditional Chinese Medicine， Shandong Binzhou 256601， China；2. Dept. of
Pharmacy， Hebei Provincial Hospital of Traditional Chinese Medicine， Shijiazhuang 050011， China；3. Dept. of
Chinese Medicine Pharmacology， Hebei University of Chinese Medicine， Shijiazhuang 050200， China）
ABSTRACT OBJECTIVE To explore the impact and mechanism of curcumin on endometriosis （EMS） model rats based on
Notch1 signaling pathway. METHODS Female SD rats with synchronized estrous cycles were implanted with autologous
endometrium on the abdominal wall to construct EMS model. EMS rats were randomly divided into model group， low-， medium-
and high-dose groups of curcumin （60， 120， 240 mg/kg）， and Notch 1 inhibitor DAPT group （7 mg/kg）. The sham surgery group
was also established， with 10 rats in each group. Rats in each group received intragastric administration or injection via caudal veins
with the corresponding drugs for 4 weeks. Endometriotic lesions were observed and measured using ultrasound and visual
inspection， and their volumes were calculated. Histopathological morphology of the lesion tissues was observed. The levels of
interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） in the abdominal cavity fluid， as well as the mRNA and
protein expression levels of Notch1， matrix metalloproteinase-9 （MMP-9）， and vascular endothelial growth factor （VEGF） in the
endometriotic lesions were measured. RESULTS Compared with the model group， the volume of endometriotic lesions in the
low- ， medium- and high-dose groups of curcumin and the DAPT group was significantly decreased （P＜0.05）； atrophy or
disappearance of columnar epithelium， cyst disappearance； the levels of IL-1β， IL-6， and TNF- α （except for the low-dose
curcumin group） in the abdominal cavity fluid， as well as the mRNA （except for MMP-9 and VEGF in the low-dose curcumin
group） and protein （except for MMP-9 in the low-dose curcumin group） expression levels of Notch1， MMP-9， and VEGF in the
endometriotic lesions were significantly decreased （P＜0.05）. The curcumin high-dose group and DAPT group showed superior
results in most indicators compared to the curcumin low- and medium-dose groups. CONCLUSIONS Curcumin has an improving
effect on EMS， and its mechanism may be related to inhibiting
Δ 基金项目 河北省自然科学基金项目（No.H2020423222）；山东
Notch1 signaling pathway， reducting local inflammatory
省中医药科技项目（No.2021M048）；河北省中医药管理局科研计划项
responses， and inhibiting ectopic endometrial invasion and
目（No.2022066）
＊第一作者 副主任医师，硕士。研究方向：妇科基础及临床。E- angiogenesis.
mail：qcm1226@163.com KEYWORDS endometriosis； curcumin； Notch1 signaling
# 通信作者 教授，硕士生导师。研究方向：中药药效物质。E- pathway
mail：323240022@qq.com

· 2744 · China Pharmacy 2024 Vol. 35 No. 22 中国药房 2024年第35卷第22期