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雌二醇戊酸酯诱导多囊卵巢综合征中阿米替林的潜在作用研究。

An investigation of the potential effects of amitriptyline on polycystic ovary syndrome induced by estradiol valerate.

机构信息

Department of Basic Medical Science, Faculty of Dentistry, Nevşehir Hacı Bektaş Veli University, Nevşehir, Turkey.

Department of Histology and Embryology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey.

出版信息

Histochem Cell Biol. 2023 Jul;160(1):27-37. doi: 10.1007/s00418-023-02188-3. Epub 2023 Mar 27.

DOI:10.1007/s00418-023-02188-3
PMID:36971834
Abstract

Polycystic ovarian syndrome (PCOS) is frequently observed in adolescent women and usually progresses with depression. The aim of this study was to examine the effects of amitriptyline (Ami), a drug used in the treatment of depression, in individuals with PCOS. Forty 12-week-old female Wistar albino rats were randomly divided into five groups: control, sham, PCOS, Ami, and PCOS + Ami. To induce the syndrome in the PCOS groups, a single dose of 4 mg/kg estradiol valerate was administered by intraperitoneal injection; 10 mg/kg Ami was administered by intraperitoneal injection for 30 days in the Ami groups. After 30 days, all the animals were sacrificed and blood, ovary, and brain tissues were collected and subjected to routine tissue processing. Stereological, histopathological analyses were performed on the ovarian sections, while luteinizing hormone (LH), follicle-stimulating hormone (FSH), catalase (CAT), and superoxide dismutase (SOD) levels were investigated in blood samples. The volume of the corpus luteum and preantral follicles increased in the PCOS group, while a decrease was determined in the number of antral follicles using stereological methods. Biochemical analysis revealed that FSH levels increased and CAT enzyme levels decreased in the PCOS group. Significant morphological changes were observed in ovaries from the PCOS group. The volume of the corpus luteum in the PCOS + Ami group decreased compared to the PCOS group. Serum FSH levels decreased in the PCOS + Ami group, while CAT enzyme levels increased compared to the PCOS group. Degenerative areas were also seen in the PCOS + Ami group ovaries. Ami administration was unable to sufficiently ameliorate the morphological and biochemical changes caused in the ovarian tissues by PCOS. In addition, this study is one of the few studies examining the effects of amitriptyline, an antidepressant frequently used in depression treatment of individuals with PCOS. We also observed firstly that use of amitriptyline caused PCOS-like ovarian morphology in healthy rat ovaries, while it had a healing effect by volume decreasing of cystic structures in the ovary with PCOS.

摘要

多囊卵巢综合征(PCOS)在青春期女性中较为常见,且通常伴有抑郁进展。本研究旨在探讨阿米替林(Ami),一种常用于治疗抑郁症的药物,对 PCOS 患者的影响。将 40 只 12 周龄雌性 Wistar 白化大鼠随机分为五组:对照组、假手术组、PCOS 组、阿米替林组和 PCOS+阿米替林组。为诱导 PCOS 综合征,PCOS 组腹腔注射 4mg/kg 戊酸雌二醇单次剂量;阿米替林组腹腔注射 10mg/kg 阿米替林 30 天。30 天后,所有动物均被处死,采集血液、卵巢和脑组织,并进行常规组织处理。对卵巢切片进行立体学和组织病理学分析,同时检测血液样本中的黄体生成素(LH)、卵泡刺激素(FSH)、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)水平。使用立体学方法发现,PCOS 组的黄体和窦前卵泡体积增加,而窦卵泡数量减少。生化分析显示,PCOS 组 FSH 水平升高,CAT 酶水平降低。PCOS 组卵巢出现明显的形态学变化。PCOS+阿米替林组的黄体体积与 PCOS 组相比减小。PCOS+阿米替林组血清 FSH 水平降低,CAT 酶水平升高。PCOS+阿米替林组卵巢也出现退行性区域。阿米替林给药不能充分改善 PCOS 引起的卵巢组织的形态和生化变化。此外,本研究是为数不多的研究阿米替林对 PCOS 患者抑郁症治疗中常用的抗抑郁药的影响的研究之一。我们还首次观察到,使用阿米替林会导致健康大鼠卵巢出现类似于 PCOS 的卵巢形态,而在患有 PCOS 的卵巢中,通过减少囊性结构的体积,阿米替林具有治疗作用。

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Klotho-Mediated Changes in Shelterin Complex Promote Cytotoxic Autophagy and Apoptosis in Amitriptyline-Treated Hippocampal Neuronal Cells.Klotho 介导的庇护素复合物变化促进阿米替林处理的海马神经元细胞中的细胞毒性自噬和细胞凋亡。
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三苯环类抗抑郁药阿米替林暴露后斑马鱼(Danio rerio)胚胎中抗氧化和生物转化酶的 mRNA 表达。
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