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代谢综合征低雌激素大鼠的膀胱功能障碍在羊水干细胞治疗后可得到改善。

Bladder dysfunction in hypoestrogenic rats with metabolic syndrome can be ameliorated after amniotic fluid stem cell treatment.

作者信息

Liang Ching-Chung, Shaw Steven W, Hsieh Wu-Chiao, Huang Yung-Hsin, Liang Chu-Ya, Lee Tsong-Hai

机构信息

Female Urology Section, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan 333, Taiwan.

College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.

出版信息

Stem Cells Transl Med. 2025 Mar 18;14(3). doi: 10.1093/stcltm/szae100.

DOI:10.1093/stcltm/szae100
PMID:40167277
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11959541/
Abstract

BACKGROUND

Bladder dysfunction may occur with high frequency in postmenopausal women with metabolic syndrome (MetS). This study evaluated the therapeutic effects of human amniotic fluid stem cells (hAFSCs) on bladder dysfunction in ovariectomized rats with MetS.

MATERIALS AND METHODS

Forty-eight female rats were divided into 4 groups: normal control, ovariectomy (OVX), and OVX and MetS without (OVX + MetS) and with hAFSCs treatment (OVX + MetS + hAFSCs). We assessed cystometric parameters, serum biochemistry parameters, wall thickness of iliac artery, apoptotic cells and collagen volume in bladder tissues, and the expressions of purinergic and muscarinic receptors, apoptosis-associated mitochondrial proteins, and markers of inflammation, fibrosis, and oxidative stress at posttreatment 1 and 3 months.

RESULTS

OVX + MetS rats showed significant dysfunction of bladder storage, including reduced intercontraction intervals and bladder capacity, along with increased residual urine volume and nonvoiding contractions. There was a significant increase in iliac artery wall thickness, bladder collagen volume, and number of apoptotic cells. Also, there were elevated expressions of P2X3 purinergic and M2/M3 muscarinic receptors, pro-apoptotic proteins, and markers of inflammation, fibrosis, and oxidative stress, with a concurrent decrease in anti-apoptotic protein, Bcl-2. Treatment with hAFSCs helped restoring bladder function, ameliorating histological abnormalities, and reducing pathological markers at 1 and/or 3 months.

CONCLUSION

These findings suggest that hAFSCs can effectively mitigate bladder dysfunction in rats with ovarian hormone deficiency and MetS by modulating oxidative stress and mitochondrial apoptotic pathways.

摘要

背景

膀胱功能障碍可能在患有代谢综合征(MetS)的绝经后女性中高频发生。本研究评估了人羊水干细胞(hAFSCs)对患有MetS的去卵巢大鼠膀胱功能障碍的治疗效果。

材料与方法

48只雌性大鼠分为4组:正常对照组、去卵巢组(OVX)、去卵巢且无hAFSCs治疗的MetS组(OVX + MetS)和去卵巢且有hAFSCs治疗的MetS组(OVX + MetS + hAFSCs)。我们在治疗后1个月和3个月评估了膀胱测压参数、血清生化参数、髂动脉壁厚度、膀胱组织中的凋亡细胞和胶原体积,以及嘌呤能和毒蕈碱受体的表达、凋亡相关线粒体蛋白、炎症、纤维化和氧化应激标志物。

结果

OVX + MetS大鼠表现出明显的膀胱储尿功能障碍,包括收缩间期缩短和膀胱容量减小,同时残余尿量增加和无排尿收缩。髂动脉壁厚度、膀胱胶原体积和凋亡细胞数量显著增加。此外,P2X3嘌呤能和M2/M3毒蕈碱受体、促凋亡蛋白以及炎症、纤维化和氧化应激标志物的表达升高,同时抗凋亡蛋白Bcl-2减少。hAFSCs治疗有助于在1个月和/或3个月时恢复膀胱功能、改善组织学异常并降低病理标志物。

结论

这些发现表明,hAFSCs可通过调节氧化应激和线粒体凋亡途径有效减轻卵巢激素缺乏和MetS大鼠的膀胱功能障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a392/11959541/06e81a1890e6/szae100_fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a392/11959541/843c61c3fde7/szae100_fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a392/11959541/36b05e00fa44/szae100_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a392/11959541/7cf41bd4fb9f/szae100_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a392/11959541/21ba1016ac99/szae100_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a392/11959541/c0a6d482ae76/szae100_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a392/11959541/63d26af619ba/szae100_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a392/11959541/06e81a1890e6/szae100_fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a392/11959541/843c61c3fde7/szae100_fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a392/11959541/36b05e00fa44/szae100_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a392/11959541/7cf41bd4fb9f/szae100_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a392/11959541/21ba1016ac99/szae100_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a392/11959541/c0a6d482ae76/szae100_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a392/11959541/63d26af619ba/szae100_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a392/11959541/06e81a1890e6/szae100_fig6.jpg

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本文引用的文献

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Int J Mol Sci. 2024 Jul 30;25(15):8310. doi: 10.3390/ijms25158310.
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Metabolic Disorders in Menopause.更年期的代谢紊乱
Metabolites. 2022 Oct 8;12(10):954. doi: 10.3390/metabo12100954.
3
Metabolic Syndrome and Overactive Bladder Syndrome May Share Common Pathophysiologies.代谢综合征与膀胱过度活动症可能具有共同的病理生理学机制。
Biomedicines. 2022 Aug 12;10(8):1957. doi: 10.3390/biomedicines10081957.
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Human amniotic fluid stem cell therapy can help regain bladder function in type 2 diabetic rats.人羊水干细胞疗法有助于恢复2型糖尿病大鼠的膀胱功能。
World J Stem Cells. 2022 May 26;14(5):330-346. doi: 10.4252/wjsc.v14.i5.330.
5
Human amniotic fluid stem cells can alleviate detrusor dysfunction caused by bladder outlet obstruction in rats.人羊水干细胞可缓解大鼠膀胱出口梗阻所致逼尿肌功能障碍。
Sci Rep. 2022 Apr 23;12(1):6679. doi: 10.1038/s41598-022-10640-y.
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Human amniotic fluid stem cells can improve cerebral vascular remodelling and neurological function after focal cerebral ischaemia in diabetic rats.人羊膜干细胞可改善糖尿病大鼠局灶性脑缺血后脑血管重塑和神经功能。
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