基于Notch1-Hes1-Prdx蛋白家族通路探究强骨胶囊治疗绝经后骨质疏松的炎症及氧化应激机制

doi:10.20047/j.issn1673-7210.2023.23.02

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Abstract

Objective To explore the mechanism of inflam- mation and oxidative stress of Qianggu Capsules in the treatment of postmenopausal osteoporosis (PMOP) based on Notch1- Hes1-Prdx protein family pathway. Methods Sixty five- month-old specific pathogen free female SD rats with body mass of (300 ± 20) g were divided into sham operation group, model control group, positive control group, and Qianggu Capsules low, medium, and high dose groups of by random number table method, with 10 rats in each group. Except for the sham operation group, the PMOP model was established by bilateral ovaries resection, and only peripheral adipose tissue of bilateral ovaries was removed in the sham operation group. The positive control group was subcutaneously injected with 200 μg/kg Estradiol, twice a week. Qianggu Capsules low, medium, and high dose groups were given 100, 200, and 300 mg/(kg·d) Qianggu Capsules by gavage, respectively; the sham operation group and model control group was given the same amount of physiological saline by gavage, the treatment lasted for 12 weeks. Bone mineral density (BMD) value, plasma inflammatory markers (interleukin [IL]-1β, IL-6, IL-8, IL-17, tumor necrosis factor-α [TNF-α]), oxidative stress markers(monoamine oxidase-A [MAOA], total antioxidant capacity [T-AOC], advanced oxidation protein products [AOPP], superoxide dismutase [SOD] ), and the protein expression level of Jagged1, Notch1, Hes1, and Prdx protein family (Prdx1-6) were compared among all groups; the mRNA and protein expressions of Jagged1, Notch1, Hes1, and Prdx1-6 in peripheral blood mononuclear cells (PBMC) and bone tissue were determined by RT-qPCR and Western blot. Results Compared with sham operation group, BMD value, T-AOC, and SOD levels of rats were decreased, IL-1β, IL-6, IL-8, IL-17, TNF-α, MAOA, and AOPP levels of rats were increased; the expression levels of Jagged1, Notch1, and Hes1 in plasma, PBMC, and bone tissue of rats were increased, while the expression levels of Prdx1 and Prdx6 of rats were decreased in model control group (P＜0.05). Compared with model control group, BMD value, T-AOC, and SOD levels of rats were increased, IL-1β, IL-6, IL-8, IL-17, TNF-α, MAOA, and AOPP levels of rats were decreased; the expression levels of Jagged1, Notch1, and Hes1 in plasma, PBMC, and bone tissue of rats were decreased, while the expression levels of Prdx1 and Prdx6 of rats were increased in Qianggu Capsules medium and high dose groups (P＜0.05). Compared with Qiangu Capsules low dose group, BMD value, T-AOC, and SOD levels of rats were increased, while IL-1β, IL-6, IL-8, IL-17, TNF-α, MAOA, and AOPP levels of rats were decreased; the expression levels of Jagged1, Notch1, and Hes1 in plasma, PBMC, and bone tissue of rats were decreased, while the expression levels of Prdx1 and Prdx6 of rats were increased in Qianggu Capsules medium and high dose groups (P＜0.05). Compared with Qianggu Capsules medium dose group, BMD value, T-AOC, and SOD levels of rats were increased, IL-1β, IL-6, IL-8, IL-17, TNF-α, MAOA, and AOPP levels of rats were decreased; the expression levels of Jagged1, Notch1, and Hes1 in plasma, PBMC, and bone tissue of rats were decreased, while the expression levels of Prdx1 and Prdx6 of rats were increased in Qiangu Capsules highdose group (P＜0.05). There were no significant differences in PRDX2-5 expressions in plasma, PBMC, and bone tissue of rats among all groups (P＞0.05). Conclusion Qianggu Capsules may down-regulate the expressions of Jagged1, Notch1, and Hes1 and up-regulate the expressions of Prdx1 and Prdx6 by inhibiting the Notch1-Hes1-Prdx signaling pathway, thus enhancing the antioxidant stress ability and improving the inflammatory response to play an anti-osteoporosis role , and the effect of Qianggu Capsules were dose-dependent.

Key words： Qianggu Capsules Notch1-Hes1-Prdx protein family pathway Postmenopausal osteoporosis Inflammation Oxidative stress

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	LU Lin1 FANG Hong2

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LU Lin1 FANG Hong2. Exploration on the mechanism of inflammation and oxidative stress of Qianggu Capsules in the treatment of postmenopausal osteoporosis based on the Notch1-Hes1-Prdx protein family pathway[J]. 中国医药导报, 2023, 20(23): 8-15.

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https://www.yiyaodaobao.com.cn/EN/10.20047/j.issn1673-7210.2023.23.02 OR https://www.yiyaodaobao.com.cn/EN/Y2023/V20/I23/8

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