烟酰胺单核苷酸通过抑制 NLRP3 介导的卵巢颗粒细胞焦亡来改善 POI 的卵巢储备功能。

Nicotinamide mononucleotide improves the ovarian reserve of POI by inhibiting NLRP3-mediated pyroptosis of ovarian granulosa cells.

机构信息

Institute of Clinical Anatomy & Reproductive Medicine, Department of Histology and Embryology Hengyang Medical School, University of South China Hengyang, 421001, Hunan, China.

Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi, Department of Obstetrics and Gynecology, Department of Reproductive Medicine Center, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China.

出版信息

J Ovarian Res. 2024 Nov 26;17(1):236. doi: 10.1186/s13048-024-01534-w.

DOI:10.1186/s13048-024-01534-w

PMID:39593096

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11590476/

Abstract

BACKGROUND

Premature ovarian insufficiency (POI) is a common clinical problem, but there is currently no effective treatment. NLRP3 inflammasome-induced pyroptosis is thought to be a possible mechanism of POI. Nicotinamide mononucleotide (NMN) has a certain anti-inflammatory effect, providing a promising approach for the treatment of POI.

METHODS

Thirty female Sprague Dawley rats were randomly divided into a control group (n = 10) and a POI group (n = 20). Cyclophosphamide (CTX) was administered for 2 weeks to induce POI. Then the POI group was divided into two groups: the CTX-POI group (n = 10), which was given saline; and the CTX-POI + NMN group (n = 10), which was given NMN at a dose of 500 mg/kg/day for 21 consecutive days. At the end of the study, the serum hormone concentrations of each group were determined, and each group was subjected to biochemical, histopathological, and immunohistochemical analyses. In the in vitro experiment, cell pyroptosis was simulated by using lipopolysaccharide (LPS) and nigricin (Nig), and then KGN cells were treated with NMN, MCC950, and AGK2, and the levels of Nicotinamide adenine dinucleotide (NAD) and inflammatory factors Interleukin-18(IL-18) and Interleukin-1β(IL-1β) in the cell supernatants were detected, and the levels of pyroptosis-related factors in the cells were determined.

RESULTS

In POI rats, NMN treatments can improve blood hormone levels and partially improve the number of follicles, enhance ovarian reserve function and ovarian index.The evidence is that the increase in NAD levels and the activation of SIRT2 expression can reduce the expression of NLRP3, Gasdermin D (GSDMD), Caspase-1, IL-18, and IL-1β in the ovary.

CONCLUSION

NMN improves CTX-induced POI by inhibiting NLRP3-mediated pyroptosis, providing a new therapeutic strategy and drug target for clinical POI patients.

摘要

背景

卵巢早衰（POI）是一种常见的临床问题，但目前尚无有效的治疗方法。NLRP3 炎性小体诱导的细胞焦亡被认为是 POI 的一种可能机制。烟酰胺单核苷酸（NMN）具有一定的抗炎作用，为 POI 的治疗提供了一种有前景的方法。

方法

将 30 只雌性 Sprague Dawley 大鼠随机分为对照组（n = 10）和 POI 组（n = 20）。用环磷酰胺（CTX）处理 2 周以诱导 POI。然后将 POI 组分为两组：CTX-POI 组（n = 10），给予生理盐水；CTX-POI + NMN 组（n = 10），给予 NMN 500 mg/kg/天，连续 21 天。研究结束时，测定各组血清激素浓度，并对各组进行生化、组织病理学和免疫组织化学分析。在体外实验中，用脂多糖（LPS）和 Nig 模拟细胞焦亡，然后用 NMN、MCC950 和 AGK2 处理 KGN 细胞，检测细胞上清液中烟酰胺腺嘌呤二核苷酸（NAD）和炎性因子白细胞介素-18（IL-18）和白细胞介素-1β（IL-1β）的水平，并测定细胞中焦亡相关因子的水平。