Kuntai capsule combined with stem cell therapy attenuates oxidative stress damage in rats with premature ovarian failure by Nrf2-ARE sig-naling pathway
10.3969/j.issn.1000-4718.2025.03.017
- VernacularTitle:坤泰胶囊联合干细胞治疗通过Nrf2-ARE信号通路减轻卵巢早衰大鼠氧化应激损伤
- Author:
Ning ZHANG
1
;
Xiaoqian WU
1
;
Yuqin HU
1
;
Geng TIAN
1
Author Information
1. 石家庄市第四医院,河北 石家庄 050011
- Publication Type:Journal Article
- Keywords:
Kuntai capsule;
stem cells;
Nrf2-ARE signaling pathway;
premature ovarian failure;
oxidative stress
- From:
Chinese Journal of Pathophysiology
2025;41(3):562-568
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the effects of Kuntai capsule combined with stem cell therapy on oxidative stress damage in rats with premature ovarian failure(POF),focusing on the Nrf2-ARE signaling pathway.METHODS:Bone marrow mesenchymal stem cells(BMSCs)from Sprague-Dawley rats were cultured from primary to third generation.Female Sprague-Dawley rats were selected,and mesenchymal stem cells were isolated.A POF rat model was established through intraperitoneal injection of cyclic phosphamide,and the model was randomly divided into five groups:POF group,Kuntai group,stem cell group,combination group,and combination+Brusatol group.Normal rats injected with physio-logical saline served as the control group,with 10 rats in each group.After the intervention,changes in body weight and ovarian index were analyzed.Serum levels of estrogen indicators[luteinizing hormone(LH),follicle-stimulating hormone(FSH),serum estradiol(E2),and anti-Müllerian hormone(AMH)]and oxidative stress markers[malondialdehyde(MDA),glutathione(GSH),and superoxide dismutase(SOD)]were measured.Ovarian tissue was isolated for histologi-cal examination using HE staining and for expression analysis of anti-apoptotic BCL-2 and pro-apoptotic BAX mRNA via RT-qPCR.Western blot analysis was conducted to assess the expression of Nrf2 and heme oxygenase-1(HO-1)proteins.RESULTS:Compared to the control group,the POF group exhibited fewer mature follicles and disorganized ovarian mor-phology,along with significantly reduced body weight gain,ovarian index,E2,AMH,SOD and GSH levels,BCL-2 mRNA,and Nrf2 and HO-1 protein expression.Conversely,LH,FSH,MDA levels,and BAX mRNA expression were significantly increased(P＜0.05).In comparison to the POF group,the Kuntai group,stem cell group,and combination group showed improved ovarian morphology,with the combination group demonstrating the most significant improvement.In these groups,body weight gain,ovarian index,E2,AMH,SOD,GSH levels,BCL-2 mRNA,and Nrf2 and HO-1 pro-tein expression were markedly increased,while LH,FSH,MDA levels,and BAX mRNA expression were notably de-creased,with significant statistical differences observed between the combination group and the Kuntai and stem cell groups(P＜0.05).In contrast,the combination+Brusatol group exhibited a reduction in mature follicles and disrupted follicular structure compared to the combination group,along with decreased body weight gain,ovarian index,E2,AMH,SOD and GSH levels,BCL-2 mRNA,and Nrf2 and HO-1 protein expression,while LH,FSH and MDA levels,and BAX mRNA expression were significantly increased(P＜0.05).CONCLUSION:The combination of Kuntai capsule and stem cell therapy effectively mitigates oxidative stress damage in POF rats,potentially through the activation of the Nrf2-ARE signaling pathway.
