Hegab Islam Ibrahim, El-Horany Hemat El-Sayed, Abd-Ellatif Rania Nagi, Nasef Nahla Anas, Okasha Asmaa H, Emam Marwa Nagy, Hassan Shereen, Elseady Walaa S, Radwan Doaa A, ElEsawy Rasha Osama, Hafez Yasser Mostafa, Hassan Maha Elsayed, Mansour Nouran Mostafa, Abdelkader Gamaleldien Elsayed, Fouda Mohamed H, Abd El Maged Amira M, Abdallah Hanan M
Physiology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt.
Bio-Physiology Department, Ibn Sina National College for Medical Studies, Jeddah 21442, Saudi Arabia.
Int J Mol Sci. 2024 Dec 24;26(1):1. doi: 10.3390/ijms26010001.
Polycystic ovarian syndrome (PCOS) is a multifaceted metabolic and hormonal disorder in females of reproductive age, frequently associated with cardiac disturbances. This research aimed to explore the protective potential of adropin and/or tirzepatide (Tirze) on cardiometabolic aberrations in the letrozole-induced PCOS model. Female Wistar non-pregnant rats were allotted into five groups: CON; PCOS; PCOS + adropin; PCOS + Tirze; and PCOS + adropin+ Tirze. The serum sex hormones, glucose, and lipid profiles were securitized. Cardiac phosphorylated levels of AKT(pAKT), glycogen synthase kinase-3 beta (pGSK-3β), NOD-like receptor family pyrin domain containing 3 (NLPR3), IL-1β and IL-18 were assayed. The cardiac redox status and endoplasmic reticulum stress (ER) parameters including relative glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) gene expressions were detected. Finally, the immunoreactivity of cardiac NF-κB, Bcl2, and BAX were assessed. Our results displayed that adropin and/or Tirze intervention successfully alleviated the PCOS-provoked cardiometabolic derangements with better results recorded for the combination treatment. The synergistic effect of adropin and Tirze is mostly mediated via activating the cardiac Akt, which dampens the GSK3β/NF-κB/NLRP3 signaling pathway, with a sequel of alleviating oxidative damage, inflammatory response, ER stress, and related apoptosis, making them alluring desirable therapeutic targets in PCOS-associated cardiac complications.
多囊卵巢综合征（PCOS）是一种发生在育龄女性中的多方面代谢和激素紊乱疾病，常与心脏功能紊乱相关。本研究旨在探讨阿多品和/或替尔泊肽（Tirze）对来曲唑诱导的PCOS模型中心血管代谢异常的保护作用。将雌性Wistar未孕大鼠分为五组：对照组；PCOS组；PCOS + 阿多品组；PCOS + Tirze组；以及PCOS + 阿多品 + Tirze组。检测血清性激素、血糖和血脂水平。测定心脏中磷酸化的AKT（pAKT）、糖原合酶激酶-3β（pGSK-3β）、NOD样受体家族含吡啉结构域3（NLPR3）、IL-1β和IL-18的水平。检测心脏氧化还原状态和内质网应激（ER）参数，包括相对葡萄糖调节蛋白78（GRP78）和C/EBP同源蛋白（CHOP）基因表达。最后，评估心脏中NF-κB、Bcl2和BAX的免疫反应性。我们的结果显示，阿多品和/或Tirze干预成功缓解了PCOS引发的心血管代谢紊乱，联合治疗效果更佳。阿多品和Tirze的协同作用主要通过激活心脏Akt介导，从而抑制GSK3β/NF-κB/NLRP3信号通路，继而减轻氧化损伤、炎症反应、内质网应激和相关凋亡，使其成为PCOS相关心脏并发症中颇具吸引力的治疗靶点。
