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阿洛福韦-1 通过抑制 NLRP3/caspase-1/IL-1β/IL-18 信号通路改善雌激素缺乏诱导的骨质疏松症。

Alloferon-1 ameliorates estrogen deficiency-induced osteoporosis through dampening the NLRP3/caspase-1/IL-1β/IL-18 signaling pathway.

机构信息

School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, Jiangsu, China.

School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, Jiangsu, China.

出版信息

Int Immunopharmacol. 2023 Nov;124(Pt B):110954. doi: 10.1016/j.intimp.2023.110954. Epub 2023 Sep 22.

DOI:10.1016/j.intimp.2023.110954
PMID:37742365
Abstract

Alloferon-1 is an insect polypeptide that has anti-inflammatory, antitumor and antiviral activity. This study aimed to determine the effects of alloferon-1 on estrogen deficiency-induced osteoporosis and explore the associated mechanism using a murine model of ovariectomy (OVX)-induced osteoporosis. Results showed that alloferon-1 prevented ovariectomy‑induced body weight gain, bone loss and bone mineral content reduction, affected biochemical markers of bone turnover, and restored the microstructure of bone trabeculae. Moreover, alloferon-1 suppressed the expression of the ovariectomy‑mediated inflammatory cytokines in the vertebrae bone tissues, including nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 (NLRP3), cysteinyl aspartate specific proteinase-1 (Caspase-1), interleukin 1β (IL-1β) and interleukin 18 (IL-18) which were determined by immunofluorescence staining and western blot. Overall, the present study provides evidence for the effectiveness of alloferon-1 against estrogen deficiency-induced osteoporosis, suggesting an alternative drug or an auxiliary modulator for the treatment of postmenopausal osteoporosis (PMOP).

摘要

阿洛福韦-1 是一种昆虫多肽,具有抗炎、抗肿瘤和抗病毒活性。本研究旨在通过去卵巢(OVX)诱导的骨质疏松症小鼠模型,确定阿洛福韦-1 对雌激素缺乏引起的骨质疏松症的影响,并探讨其相关机制。结果表明,阿洛福韦-1 可预防去卵巢引起的体重增加、骨丢失和骨矿物质含量减少,影响骨转换的生化标志物,并恢复骨小梁的微观结构。此外,阿洛福韦-1 抑制了卵巢切除介导的炎症细胞因子在椎骨组织中的表达,包括核苷酸结合寡聚化结构域样受体家族富含亮氨酸重复蛋白 3(NLRP3)、半胱天冬氨酸特异性蛋白酶-1(Caspase-1)、白细胞介素 1β(IL-1β)和白细胞介素 18(IL-18),这是通过免疫荧光染色和 Western blot 确定的。总之,本研究为阿洛福韦-1 防治雌激素缺乏性骨质疏松症提供了证据,提示其可能成为治疗绝经后骨质疏松症(PMOP)的一种替代药物或辅助调节剂。

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