School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Reproductive & Women-Children Hospital, Chengdu, China.
Department of Gynecology, Leping Maternal and Child Health Care Hospital, Leping, China.
Reprod Biol. 2022 Jun;22(2):100638. doi: 10.1016/j.repbio.2022.100638. Epub 2022 Mar 28.
Primary ovarian insufficiency (POI) is a common gynecological disease. Autoimmunity is a common cause of POI. Icariin (ICA) plays a therapeutic role in many autoimmune diseases. This study aims to investigate the effect of ICA on autoimmune POI mice and its effect on immune regulation. Sixty-three female BALB/c mice were randomized into three groups (control, POI, POI + ICA). POI and POI + ICA group were hypodermically injected with zona pellucida three peptides (pZP3) to induce autoimmune POI. Then the POI + ICA group was gavaged with ICA. A vaginal smear was to observe estrous cycles, hematoxylin-eosin staining was to count follicles. Enzyme-linked immunosorbent analysis determined serum FSH, LH, AMH, and anti-zona pellucida antibody (AZPAb) levels. In addition, flow cytometry detected the expression of Th1 cells and Treg cells, and Western blot was used to detect the expression of Nuclear factor E2 related factor 2(Nrf2), heme oxygenase-1 (HO-1), and Sirtuin-1 (Sirt1) proteins. pZP3 treatment decreased serum AMH levels and increased FSH, LH, and AZPAb levels. Additionally, decreases in the number of healthy follicles at all stages and an increase in the number of atretic follicles. Abnormal ovarian structure and an arrested estrous cycle were also noted. However, ICA rescued POI through up-regulating Nrf2, HO-1, and Sirt1 expressions and up-regulating Treg expressions. ICA treatment improved the structure of the injured ovarian and its function in autoimmune POI mice. The mechanism is achieved by increasing the expression of Nrf2/HO-1/Sirt1 pathway in the ovary and increasing Treg cells' expression.
原发性卵巢功能不全（POI）是一种常见的妇科疾病。自身免疫是 POI 的常见原因。淫羊藿苷（ICA）在许多自身免疫性疾病中发挥治疗作用。本研究旨在探讨 ICA 对自身免疫性 POI 小鼠的作用及其对免疫调节的影响。将 63 只雌性 BALB/c 小鼠随机分为三组（对照组、POI 组、POI+ICA 组）。POI 组和 POI+ICA 组皮下注射透明带三肽（pZP3）诱导自身免疫性 POI。然后 POI+ICA 组给予 ICA 灌胃。阴道涂片观察动情周期，苏木精-伊红染色计数卵泡。酶联免疫吸附分析测定血清 FSH、LH、AMH 和抗透明带抗体（AZPAb）水平。此外，流式细胞术检测 Th1 细胞和 Treg 细胞的表达，Western blot 检测核因子 E2 相关因子 2（Nrf2）、血红素加氧酶-1（HO-1）和 Sirtuin-1（Sirt1）蛋白的表达。pZP3 处理降低了血清 AMH 水平，增加了 FSH、LH 和 AZPAb 水平。此外，各阶段健康卵泡数量减少，闭锁卵泡数量增加。卵巢结构异常，动情周期停滞。然而，ICA 通过上调 Nrf2、HO-1 和 Sirt1 的表达以及上调 Treg 的表达来挽救 POI。ICA 治疗改善了自身免疫性 POI 小鼠卵巢损伤的结构及其功能。其机制是通过增加卵巢中 Nrf2/HO-1/Sirt1 通路的表达和增加 Treg 细胞的表达来实现的。
