浏览全部资源
扫码关注微信
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
Published:30 November 2024,
Received:12 July 2024,
Revised:26 October 2024,
移动端阅览
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 Δ[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 Δ[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.
子宫内膜异位症姜黄素Notch1信号通路
curcuminNotch1 signaling pathway
KAPOOR R,STRATOPOULOU C A,DOLMANS M M. Pathogenesis of endometriosis:new insights into prospective therapies[J]. Int J Mol Sci,2021,22(21):11700.
MOLDOVAN G E,MIELE L,FAZLEABAS A T. Notch signaling in reproduction[J]. Trends Endocrinol Metab,2021,32(12):1044-1057.
RUMPH J T,STEPHENS V R,ARCHIBONG A E,et al. Environmental endocrine disruptors and endometriosis[J]. Adv Anat Embryol Cell Biol,2020,232:57-78.
CAI J Q,SUN H,ZHENG B,et al. Curcumin attenuates lncRNA H19-induced epithelial-mesenchymal transition in tamoxifen-resistant breast cancer cells[J]. Mol Med Rep,2021,23(1):13.
沈龙德,李爱禄,李丽春,等. 姜黄素对大鼠子宫内膜异位症影响的实验研究[J]. 中国临床药理学与治疗学,2020,25(8):862-868.
SHEN L D,LI A L,LI L C,et al. Experimental study on the effect of curcumin on endometriosis in rats[J]. Chin J Clin Pharmacol Ther,2020,25(8):862-868.
秦翠梅,聂晓博,王炎,等. 基于JAK2/STAT3信号通路探讨三棱莪术及配伍干预大鼠子宫内膜异位症的配伍研究[J]. 中药药理与临床,2022,38(1):134-139.
QIN C M,NIE X B,WANG Y,et al. Compatibility analysis of Rhizoma Sparganii and Curcumae Rhizoma on endometriosis in rats based on JAK2/STAT3 signaling pathway[J]. Pharmacol Clin Chin Mater Med,2022,38(1):134-139.
曹立花,李丽娟,胡晓丹,等. 姜黄素对子宫内膜异位症大鼠PI3K/AKT/GSK-3β通路及肥大细胞活化的影响[J]. 中国免疫学杂志,2021,37(4):480-485.
CAO L H,LI L J,HU X D,et al. Effects of curcumin on PI3K/AKT/GSK-3β pathway and mast cell activation in endometriosis rats[J]. Chin J Immunol,2021,37(4):480-485.
陈雪,石亚琳,孙合圣,等. 基于Notch信号通路探讨柚皮素调节Th17/Treg平衡治疗哮喘的机制研究[J]. 中国免疫学杂志,2023,39(7):1383-1389.
CHEN X,SHI Y L,SUN H S,et al. Mechanism of naringenin in regulating Th17/Treg balance to treat asthma based on Notch signaling pathway[J]. Chin J Immunol,2023,39(7):1383-1389.
NISHAD R,MESHRAM P,SINGH A K,et al. Activation of Notch1 signaling in podocytes by glucose-derived AGEs contributes to proteinuria[J]. BMJ Open Diabetes Res Care,2020,8(1):e001203.
韩丽丽,张文秀,刘姣. 莪术对子宫内膜异位症大鼠的改善作用[J]. 中国临床药理学杂志,2019,35(19):2328-2331.
HAN L L,ZHANG W X,LIU J. Improvement of Rhizoma zedoariae on endometriosis in rats[J]. Chin J Clin Pharmacol,2019,35(19):2328-2331.
马蓉,李娟,王芳. 姜黄素通过降低miR-135b-5p和FEN1表达增强卵巢癌OVCAR-3细胞顺铂敏感性[J]. 江苏大学学报(医学版),2024,34(4):324-330.
MA R,LI J,WANG F. Curcumin enhances cisplatin sensitivity of OVCAR-3 cells by decreasing the expression of miR-135b-5p and FEN1[J]. J Jiangsu Univ Med Ed,2024,34(4):324-330.
汪洁,杨彩凤,吴亚凡,等. 姜黄素通过调控Notch1通路对人子宫内膜癌ISH细胞株孕激素治疗敏感性的影响[J]. 西部医学,2022,34(5):688-693.
WANG J,YANG C F,WU Y F,et al. Effect of curcumin on the sensitivity of human endometrial carcinoma ISH cell line to progesterone therapy by regulating Notch1 pathway[J]. Med J West China,2022,34(5):688-693.
ZHOU B H,LIN W L,LONG Y L,et al. Notch signaling pathway:architecture,disease,and therapeutics[J]. Signal Transduct Target Ther,2022,7(1):95.
廖源,王开举,李浩僡,等. 雌激素调控子宫内膜异位症基质细胞侵袭和迁移的机制研究[J]. 局解手术学杂志,2023,32(8):673-679.
LIAO Y,WANG K J,LI H H,et al. Mechanism of estrogen regulating the invasion and migration of endometriosis stromal cells[J]. J Reg Anat Oper Surg,2023,32(8):673-679.
SONG Y,SU R W,JOSHI N R,et al. Interleukin-6(IL-6)activates the NOTCH1 signaling pathway through E-proteins in endometriotic lesions[J]. J Clin Endocrinol Metab,2020,105(5):1316-1326.
KÖRBEL C,GERSTNER M D,MENGER M D,et al. Notch signaling controls sprouting angiogenesis of endometriotic lesions[J]. Angiogenesis,2018,21(1):37-46.
0
Views
0
下载量
0
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution