Exploring the Effects of Quyu Jiedu Formula （祛瘀解毒方） on the Ectopic Tissues of the Rat Uterus in An Endometriosis Model Based on Iron Autophagy Mediated by the NCOA4/NF-κB Signalling Pathway
10.13288/j.11-2166/r.2024.06.013
- VernacularTitle:基于NCOA4/NF-κB信号通路介导的铁自噬探讨祛瘀解毒方对子宫内膜异位症模型大鼠子宫异位组织的影响
- Author:
Yiming LIU
1
;
Zhihong LIU
2
;
Fang LIAN
3
Author Information
1. The First School of Clinical Medicine， Shandong University of Traditional Chinese Medicine， Jinan， 250000
2. Shandong College Of Traditional Chinese Medicine
3. The Affiliated Hospital of Shandong University of Traditional Chinese Medicine
- Publication Type:Journal Article
- Keywords:
endometriosis;
Quyu Jiedu Formula （祛瘀解毒方）;
iron autophagy;
inflammation;
nuclear receptor co-activator factor 4;
nuclear factor κB
- From:
Journal of Traditional Chinese Medicine
2024;65(6):627-635
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the possible mechanism of Quyu Jiedu Formula （祛瘀解毒方） in the treatment of endometriosis in terms of iron autophagy mediated by nuclear receptor coactivator 4/nuclear factor κB （NCOA4/NF-κB） signalling pathway. MethodsFifty female SD rats were randomly divided into sham surgery group， model group， mifepristone group， low- and high-dose Quyu Jiedu Formula group， with 10 rats in each group. In the sham surgery group， only operation of opening and closing abdomen was performed， and in the remaining groups， the rat with endometriosis was modelled by autotransplantation. On the next day after successful modelling， saline 2 ml/d was given by gavage to the sham surgery group and the model group； mifepristone 1.05 mg/（kg·d） was given by gavage to the mifepristone group； Quyu Jiedu Formula 12.23 g/（kg·d） and 48.92 g/（kg·d） were given to the low- and high-dosage Quyu Jiedu Formula groups， respectively administered for 4 weeks consecutively. In the remaining 4 groups， all ectopic endometrial tissues were removed from the rats. The volume of ectopic lesions was measured in the model group， the mifepristone group， and the low- and high-dose Quyu Jiedu Formula groups， and the pathological changes of endometrial/ectopic tissues were observed by HE staining， and the protein expression and expression of NCOA4， Ferritin Heavy Chain 1 （FTH1）， Panax quinquefolium （P62）， Microtubule-associated Protein 1 Light Chain 3β （LC3B）， and P-NF-κB protein expression and NCOA4， FTH1， LC3B， P62 mRNA expression were detected in the endometrium and ectopic tissues； the co-localisation of NCOA4 and LC3B， free iron content， and levels of interleukin 6 （IL-6） and tumour necrosis factor α （TNF-α） in endometrial/eutopic endometrial tissues were also detected. ResultsNo ectopic lesions were seen in the sham surgery group. The ectopic tissues of rats in the model group showed obvious pathological damage， while the pathological damage of the ectopic tissues of rats in each admi-nistration group was reduced to different degrees. Compared with the model group， the volume of ectopic lesions was reduced in the mifepristone group and the high- and low-dose Quyu Jiedu Formula groups， and the volume of ectopic lesions in the high-dose Quyu Jiedu Formula group and the mifepristone group was significantly smaller than that in the low-dose Quyu Jiedu Formula group （P＜0.01）. Compared with the sham surgery group， the ectopic tissues of the model group showed up-regulation of LC3BⅡ/LC3B I values， NCOA4， and P-NF-κB protein expression， down-regulation of P62 and FTH1 protein expression， increase in free iron content and IL-6 and TNF-α levels， and increase in the co-localisation positivity rate and co-localised cell density of NCOA4 and LC3B （P＜0.05 or P＜0.01）. Compared with the model group， the ectopic endothelial tissue LC3BⅡ/LC3BⅠ values and the expression of NCOA4 and P-NF-κB proteins were down-regulated in the low- and high-dose Quyu Jiedu Formula group and mifepristone group， the colocalisation positivity rate of NCOA4 and LC3B significantly reduced， and the content of free iron and the level of IL-6 decreased （P＜0.05 or P＜0.01）. Compared with the mifepristone group， P62 more obvious up-regulated and TNF-α level reduced in the high-dose Quyu Jiedu Formula group （P＜0.05）. Compared with the low-dose Quyu Jiedu Formula group， the free iron content of ectopic tissues and the levels of IL-6 and TNF-α reduced in the high-dose Quyu Jiedu Formula group （P＜0.01）. ConclusionThe mechanism of endometriosis treatment by Quyu Jiedu Formula may be related to the inhibition of iron autophagy mediated by the NCOA4/NF-κB signalling pathway in endometriotic tissues， which improves endometrial inflammation.
