藤黄健骨胶囊通过SIRT1/PGC-1α/Nrf2信号通路抑制绝经后骨质疏松大鼠成骨细胞凋亡

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中文摘要：藤黄健骨胶囊可以提高绝经后骨质疏松模型鼠的骨密度来改善其骨微结构损害,但具体机制尚未阐明.本文主要研究藤黄健骨胶囊抑制绝经后骨质疏松症大鼠成骨细胞凋亡与SIRT1/PGC-1α/Nrf2信号通路的关系,旨在探讨藤黄健骨胶囊对绝经后骨质疏松症的作用机制.采用去卵巢法建立绝经后骨质疏松大鼠模型,分别给予藤黄健骨胶囊(0.09、0.18、0.36 g/kg)灌胃,连续干预8周后进行指标检测.采用TUNEL染色观察股骨组织凋亡情况,结果发现,藤黄健骨胶囊各剂量组股骨组织凋亡阳性细胞和凋亡率均减少(P＜0.01).采用双重免疫荧光染色观察股骨组织成骨细胞中SIRT1、PGC-1α和Nrf2表达水平表达情况,结果发现,藤黄健骨胶囊中、高剂量组成骨细胞PGC-1α表达荧光面积明显升高,各剂量组成骨细胞SIRT1和Nrf2表达荧光面积也明显升高(P＜0.01).qPCR 和 Western 印迹检测股骨组织 SIRT1、PGC-1α、Nrf2、Runx2、Bcl-2、Caspase-3 和Caspase-9的mRNA表达水平和翻译水平变化,结果显示,藤黄健骨胶囊中、高剂量组股骨组织Runx2 mRNA水平和蛋白质水平、Nrf2蛋白质水平均明显升高,Caspase-9蛋白质水平明显下降,各剂量组股骨组织SIRT1、PGC-1α、Bcl-2 mRNA水平和蛋白质水平、Nrf2 mRNA水平也均明显升高,而其各剂量组股骨组织Caspase-3 mRNA水平、蛋白质水平和Caspase-9 mRNA水平均则明显降低(P＜0.01).综上,本研究初步揭示了藤黄健骨胶囊对绝经后骨质疏松模型鼠成骨细胞凋亡的抑制与SIRT1/PGC-1α/Nrf2信号通路有关,SIRT1可能是调控成骨细胞凋亡的重要靶点.

外文标题：Tenghuangjiangu Capsule Inhibits Osteoblast Apoptosis in Postmenopausal Osteoporosis Rats through SIRT1/PGC-1α/Nrf2 Signaling Pathway

外文摘要：Tenghuangjiangu capsules(TJC)can improve bone microstructural damage by increasing bone mineral density in postmenopausal osteoporosis model rats,but the specific mechanism has not been clarified.In this study,the effects of TJC on osteoblast apoptosis and SIRT1/PGC-1α/Nrf2 signaling pathway in postmenopausal osteoporosis rats were studied,in order to explore the mechanism of TJC on postmenopausal osteoporosis.The postmenopausal osteoporosis rat model was established using the ovariectomized method.TJC(0.09 g/kg,0.18 g/kg,0.36 g/kg)were given by intragastric administration,and the indices were detected after 8 weeks of continuous intervention.The apoptosis of femur tissue was observed by TUNEL staining.The results showed that the number of positive cells and rate of apoptosis of femur tissue decreased in each dose group(P＜0.01).The expression of SIRT1,PGC-1α and Nrf2 expression level in osteoblasts of femoral tissue was observed by double immunofluorescence staining.The fluorescent area of PGC-1α expression in osteoblasts in high dose increased significantly,and the fluorescent area of SIRT1 and Nrf2 expression in osteoblasts in each dose also increased significantly(P＜0.01).Detection of SIRT1,PGC-1α,Nrf2,Runx2,Bcl-2,Caspase-3 and Caspase-9 in femoral tissue by qPCR and Western blotting.The expression of Runx2 mRNA level and translation level,the expression of Nrf2 translation level were significantly increased,and the expression of Caspase-9 translation level were significantly decreased in the middle and high-dose groups of TJC.The expression of SIRT1,PGC-1α,Bcl-2 mRNA level and translation level,and the expression of Nrf2 mRNA level were also significantly increased at each dose,while the expression of Caspase-3 mRNA level and translation level were significantly decreased,and the expression of Caspase-9 mRNA level were significantly decreased at each dose(P＜0.01).Thus,this study preliminarily revealed that the inhibition of osteoblast apoptosis in postmenopausal osteoporosis model rats by TJC involves the SIRT1/PGC-1α/Nrf2 signaling pathway,and SIRT1 may be an important target for regulating osteoblast apoptosis.

外文关键词：

tenghuangjiangu capsule(TJC)postmenopausal osteoporosis(PMOP)SIRT1/PGC-1α/Nrf2 signaling pathwayratsosteoblastic apoptosis

作者：

安方玉、王霞霞、颜春鲁、孙柏、汪春梅、柳颖、常伟荣、宋佳眙、王玉洁、马海珍、张蕊、陈振东、袁万英

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作者单位：

甘肃中医药大学教学实验实训中心,兰州 730000

甘肃中医药大学中西医结合学院中医外科教研室,兰州 730000

甘肃省中医药研究中心,兰州 730000

甘肃中医药大学基础医学院免疫教研室,兰州 730000

甘肃中医药大学医学教学部,兰州 730000

定西市中医医院,甘肃定西 743099

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关键词：

藤黄健骨胶囊绝经后骨质疏松 SIRT1/PGC-1α/Nrf2信号通路大鼠成骨细胞凋亡

基金：

国家自然科学基金项目甘肃省中医药管理局项目甘肃省中医药管理局项目甘肃省"双一流"科研重点项目兰州市科技计划项目甘肃中医药大学研究生教育教学研究与改革项目甘肃中医药大学教学研究与改革项目甘肃中医药大学教学研究与改革项目

项目编号：

82060872GZKP-2023-39GZKP-2023-63GSSYLXM-052022-3-2215YBXM-202332ZHXM-202307

出版年：

2024

DOI：

10.13865/j.cnki.cjbmb.2024.02.1330

中国生物化学与分子生物学报

中国生物化学与分子生物学会北京大学

中国生物化学与分子生物学报

CSTPCD北大核心

影响因子：0.617

ISSN：1007-7626

年,卷(期)：2024.40(3)

参考文献量27