Study on the molecular mechanism of BuShenHuoXue capsule in treatment of steroid-induced osteonecrosis of the femoral head.

Study on the molecular mechanism of BuShenHuoXue capsule in treatment of steroid-induced osteonecrosis of the femoral head.
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补肾活血胶囊治疗激素性股骨头坏死的分子机制研究

DOI:
10.21037/atm-20-7040
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发表时间:
2020-12
影响因子:
--
通讯作者:
Li G
Li G
中科院分区:
医学4区
文献类型:
--
作者:
Li JC;Liang XZ;Luo D;Yan BZ;Liu JB;Li G

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研究背景激素性股骨头坏死(Steroid-induced osteonecrosis of the femoral head,SONFH)是由于高剂量激素导致股骨头活性成分死亡而引起的病理过程,已成为一种常见的公共卫生问题。补肾活血胶囊(BSHXC)已被临床证实对SONFH有效,其主要药理作用为补肾活血,但其作用机制尚待进一步探讨。方法采用甲基强的松龙(MPS)30 mg/kg/d,连续3 d,每周1次,共4周的方法建立大鼠股骨头坏死模型。按临床用量(淫羊藿3g,杜仲15 g,丹参30 g,甘草15 g,牛膝12 g,鹿角胶10 g,香附10 g,甘草10 g)计算。9 g,甘草9 g),换算成大鼠等效剂量,按10 mL/kg体重灌胃,每日1次。通过体内实验、SONFH药效学实验、生物信息学实验和网络药理学实验,确定BSHXC的有效成分,并对其对SONFH的保护作用进行研究;通过富集分析探讨BSHXC的可能作用机制;通过细胞实验分析BSHXC对骨髓间充质干细胞(BMSCs)成骨与凋亡相关激素的影响。结果实验证实补肾活血胶囊能有效减少SONFH大鼠模型的骨丢失。从生物信息学和由10种药物-208种药理学-126个靶点构成的网络中,富集分析显示,核心靶点为炎症反应、类固醇激素、雌激素受体、骨质疏松、成骨调节和破骨细胞分化等。细胞增殖和染色结果支持BSHXC促进成骨和干预细胞凋亡的机制。结论补肾活血胶囊通过调节相关靶点,减轻炎症反应,改变激素反应,调节雌激素受体,延缓骨质疏松,调节成骨细胞和破骨细胞分化,改善局部微环境,以多组分、多靶点、多环节的方式延缓或逆转SONFH的进展。
Background Steroid-induced osteonecrosis of the femoral head (SONFH) is the pathological process caused by the death of the active components of the head of the femur due to the high dose of hormones, which has become a common public health problem. BuShenHuoXue capsule (BSHXC) has been clinically proven to be effective against the SONFH, the main pharmacological action of BSHXC is tonifying kidney and promoting blood circulation, but the mechanism remains to be explored. Methods We established a rat SONFH model by injecting Methylprednisolone (MPS) into the right gluteus muscle 30 mg/kg/d, 3 days of continuous injection every week, 4 weeks in total. According to the clinical dosage of BSHXC (Herba epimedium 3 g, Eucommia ulmoides 15 g, Salvia miltiorrhizae 30 g, Chuanxiong 15 g, Paeonia lactiflora Pall 15 g, Poria cocos 12 g, Achyranthes bidentata 12 g, antler gum 10 g, Cyperus rotundus L. Nine g and Radix Glycyrrhizae 9 g), it was converted into the equivalent dose of rats, and gavage was performed at the weight of 10 mL/kg, once per day. The BSHXC was subjected to experiments in vivo, SONFH pharmacodynamics, bioinformatics, and network of pharmacology to determine the active ingredients, and its protective role against SONFH, Enrichment analysis was performed to explore the possible mechanism of BSHXC, and cell experiments were undertaken to analyze the impact of BSHXC on the hormones associated with bone marrow mesenchymal stem cells (BMSCs) between osteogenesis and apoptosis. Results Experiments confirmed that BSHXC could effectively reduce bone loss in SONFH rat models. From bioinformatics and a network constructed from 10 drugs-208 pharmacology-126 targets, the enrichment analysis showed that the core targets were inflammatory reaction, steroid hormones, estrogen receptors, osteoporosis, and adjustment of osteogenesis and osteoclast differentiation, among others. The cell proliferation and staining supported that the mechanism of BSHXC promoted osteogenesis and intervening in apoptosis. Conclusions The BSHXC reduced the inflammatory response, changed steroid response, regulated estrogen receptors, delayed osteoporosis, regulated osteoblast and osteoclast differentiation by regulating related targets, and improved the local microenvironment by a multi-component, multi-target, and multi-link process to delay or reverse the progression of SONFH.
DOI: 10.18632/oncotarget.18313
发表时间: 2017-11-14
期刊: Oncotarget
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