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1.滨州市中医医院妇科,山东 滨州 256601
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
Received:12 July 2024,
Revised:2024-10-26,
Accepted:28 October 2024,
Published:30 November 2024
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秦翠梅,刘心怡,丁晓兰,等.姜黄素对子宫内膜异位症模型大鼠的影响及机制[J].中国药房,2024,35(22):2744-2749.
QIN Cuimei,LIU Xinyi,DING Xiaolan,et al.Impact and mechanism of curcumin on endometriosis model rats[J].ZHONGGUO YAOFANG,2024,35(22):2744-2749.
秦翠梅,刘心怡,丁晓兰,等.姜黄素对子宫内膜异位症模型大鼠的影响及机制[J].中国药房,2024,35(22):2744-2749. DOI: 10.6039/j.issn.1001-0408.2024.22.07.
QIN Cuimei,LIU Xinyi,DING Xiaolan,et al.Impact and mechanism of curcumin on endometriosis model rats[J].ZHONGGUO YAOFANG,2024,35(22):2744-2749. DOI: 10.6039/j.issn.1001-0408.2024.22.07.
目的
2
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
2
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
2
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
2
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。
OBJECTIVE
2
To explore the impact and mechanism of curcumin on endometriosis (EMS) model rats based on Notch1 signaling pathway.
METHODS
2
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
2
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
2
Curcumin has an improving effect on EMS, and its mechanism may be related to inhibiting Notch1 signaling pathway, reducting local inflammatory responses, and inhibiting ectopic endometrial invasion and angiogenesis.
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