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沉默信息调节因子1/叉头框蛋白O轴在二至丸对去卵巢大鼠治疗作用机制中起关键作用。

Sirt1/Foxo Axis Plays a Crucial Role in the Mechanisms of Therapeutic Effects of Erzhi Pill in Ovariectomized Rats.

作者信息

Liang Wenna, Li Xihai, Li Guanhui, Hu Liu, Ding Shanshan, Kang Jie, Shen Jianying, Li Candong, Asakawa Tetsuya

机构信息

Research Base of Traditional Chinese Medicine Syndrome, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.

出版信息

Evid Based Complement Alternat Med. 2018 Aug 26;2018:9210490. doi: 10.1155/2018/9210490. eCollection 2018.

DOI:10.1155/2018/9210490
PMID:30224934
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6129318/
Abstract

. Erzhi pill (EZP), a traditional Chinese herbal formula, has been widely used to treat postmenopausal osteoporosis (PMOP) in China. However, its molecular mechanisms remain unclear. The aim of the present study is to investigate the antiosteoporotic effect of EZP on an ovariectomized rat model of PMOP. We performed the biomarkers of bone metabolism disorder, bone morphology, bone mineral density (BMD), and bone biomechanics to confirm the successful establishment of the PMOP model. We then investigated the expression of biomarkers related to the Sirt1/Foxo axis. We also examined microRNA-132 (miR-132), a regulator in the Sirtuin1 (Sirt1) expression. The bone metabolism disorder, bone morphology, BMD, and bone biomechanics in ovariectomized rats were improved by EZP administration. The antiosteoporotic effect of EZP was confirmed. We also found that the expressions of Sirt1, Runx2, Foxo1, and Foxo3a were downregulated in ovariectomized rats, while being then upregulated by EZP administration. And the expression of PPAR- and miR-132 was upregulated in ovariectomized rats and then downregulated by EZP administration. These results provided evidence that Sirt1/Foxo axis related mechanism may play a crucial role in the therapeutic effects of EZP, indicating that Sirt1/Foxo axis can be considered as a potential therapeutic target for PMOP in the future.

摘要

二至丸（EZP）是一种传统中药配方，在中国已被广泛用于治疗绝经后骨质疏松症（PMOP）。然而，其分子机制尚不清楚。本研究的目的是探讨二至丸对去卵巢大鼠PMOP模型的抗骨质疏松作用。我们检测了骨代谢紊乱的生物标志物、骨形态、骨密度（BMD）和骨生物力学，以确认PMOP模型的成功建立。然后，我们研究了与Sirt1/Foxo轴相关的生物标志物的表达。我们还检测了微小RNA-132（miR-132），它是沉默调节蛋白1（Sirt1）表达的调节因子。给予二至丸可改善去卵巢大鼠的骨代谢紊乱、骨形态、骨密度和骨生物力学。二至丸的抗骨质疏松作用得到证实。我们还发现，去卵巢大鼠中Sirt1、Runx2、Foxo1和Foxo3a的表达下调，而给予二至丸后上调。并且PPAR-和miR-132在去卵巢大鼠中的表达上调，给予二至丸后下调。这些结果提供了证据，表明Sirt1/Foxo轴相关机制可能在二至丸的治疗作用中起关键作用，表明Sirt1/Foxo轴未来可被视为PMOP的潜在治疗靶点。

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