依普利酮和非诺贝特对卵巢缺血再灌注损伤中TLR4/MYD88/NF-κB/AP1/IL-6通路的免疫调节及醛固酮/PPARα受体的调控
Immune regulation of TLR4/MYD88/ NF-κB/AP1/IL-6 pathway and modulation of aldosterone/PPARα receptors by eplerenone and fenofibrate in ovarian ischemia reperfusion induced injury.
作者信息
Refaie Marwa Monier Mahmoud, Abdel-Hakeem Elshymaa A, Shehata Sayed, Elsaghir Shereen Mohammed Mohammed, Mokhemer Sahar Ahmed, Ahmed Nagwa Zenhom Mustafa, Elsayed Samar Hisham, Mageed Aya Aly Ashraf Abdel, Mohamed Heba Reda, Shawky Heba A, Ali Doaa Mohamed Elroby
机构信息
Department of Medical Pharmacology, Faculty of Medicine, Minia University, 61511, El-Minia, Egypt; Faculty of Medicine, Minia National University, El-Minia, Egypt.
Department of Medical Physiology, Faculty of Medicine, Minia University, 61511 El-Minia, Egypt; Faculty of Medicine, Minia National University, El-Minia, Egypt.
出版信息
Int Immunopharmacol. 2025 Sep 23;162:115113. doi: 10.1016/j.intimp.2025.115113. Epub 2025 Jun 23.
BACKGROUND
The immune system is deeply involved in the pathogenesis of different gynecological disorders including ovarian torsion that commonly occurs during surgical manipulation or within ovarian masses, affecting not only the ovaries, but it has remote effect on different organs particularly cardiac tissue. Early intervention and proper medical treatment are so important to preserve the ovaries and prevent distant organ damage. Accordingly, the aim of this work was to evaluate the possible ameliorative role of eplerenone (EPL) or fenofibrate (FEN) on ovarian and cardiac affection in an experimental model of ovarian ischemia/reperfusion (OIR).
METHOD
Fifty female Wistar albino rats were divided into five groups (n = 10); control, OIR induced group, OIR plus EPL (100 mg/kg), OIR plus FEN (300 mg/kg), OIR plus EPL (100 mg/kg) plus FEN (300 mg/kg).
RESULTS
OIR could induce ovarian injury with remote cardiac damage. Data of current study revealed significant increases of the cardiac enzymes, and malondialdehyde (MDA) levels but decreases of total anti-oxidant capacity (TAC) and reduced glutathione (GSH) levels. Moreover, there were increases in toll like receptor 4 (TLR4), myeloid differentiation primary response 88 (MYD88), activation protein 1 (AP1), interleukin 6 (IL-6), nuclear factor kappa b (NF-κB) and cleaved caspase-3 with abnormal histological features. However, EPL or FEN co-administration alone or in combination reversed OIR damaging effects by antagonizing aldosterone action by EPL, anti-inflammatory, anti-oxidant, and anti-apoptotic features with modulation of peroxisome proliferator activated receptor alpha (PPARα) by FEN and TLR4/MYD88/ NF-κB/AP1/IL-6 pathway. Interestingly, co-administration of both drugs showed more improvement than giving each one alone.
CONCLUSION
EPL and/or FEN had ameliorative properties against OIR induced harmful effects.
背景
免疫系统深度参与不同妇科疾病的发病机制，包括卵巢扭转，卵巢扭转常见于手术操作期间或卵巢肿块内，不仅影响卵巢，还会对不同器官尤其是心脏组织产生远程影响。早期干预和适当的医学治疗对于保护卵巢和预防远处器官损伤非常重要。因此，本研究的目的是评估依普利酮（EPL）或非诺贝特（FEN）在卵巢缺血/再灌注（OIR）实验模型中对卵巢和心脏影响的可能改善作用。
方法
将50只雌性Wistar白化大鼠分为五组（n = 10）；对照组、OIR诱导组、OIR加EPL（100 mg/kg）组、OIR加FEN（300 mg/kg）组、OIR加EPL（100 mg/kg）加FEN（300 mg/kg）组。
结果
OIR可导致卵巢损伤并伴有远程心脏损伤。本研究数据显示心脏酶和丙二醛（MDA）水平显著升高，但总抗氧化能力（TAC）和还原型谷胱甘肽（GSH）水平降低。此外，Toll样受体4（TLR4）、髓样分化初级反应88（MYD88）、活化蛋白1（AP1）、白细胞介素6（IL-6）、核因子κB（NF-κB）和裂解的半胱天冬酶-3增加，伴有异常组织学特征。然而，单独或联合给予EPL或FEN可通过EPL拮抗醛固酮作用、抗炎、抗氧化和抗凋亡特性以及FEN对过氧化物酶体增殖物激活受体α（PPARα）和TLR4/MYD88/NF-κB/AP1/IL-6途径的调节来逆转OIR的损伤作用。有趣的是，两种药物联合使用比单独使用每种药物显示出更多改善。
结论
EPL和/或FEN对OIR诱导的有害影响具有改善作用。
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