Effect of Zuoguiwan in Improving BMD and Trabecular Bone Microarchitecture in Ovariectomy-induced Osteoporosis Rats by Regulating RANKL/OPG Pathway Mediated by β<sub>2</sub>AR

Fei-xiang LIU; Zi-xuan LIN; Dao-ming XU; Su-min YE; Ming-yue ZHANG; Qiao-ling FAN; Feng TAN; Xing LI; Yi CHAI; Cong-ying MAI; Sheng-feng LU

doi:10.13422/j.cnki.syfjx.20191524

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Effect of Zuoguiwan in Improving BMD and Trabecular Bone Microarchitecture in Ovariectomy-induced Osteoporosis Rats by Regulating RANKL/OPG Pathway Mediated by β₂AR

Topic on Tonifying Kidney, Benefiting Essence, Filling Marrow and Strengthening Bone Effects of Zuoguiwan | 更新时间：2021-02-09

- Effect of Zuoguiwan in Improving BMD and Trabecular Bone Microarchitecture in Ovariectomy-induced Osteoporosis Rats by Regulating RANKL/OPG Pathway Mediated by β₂AR
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 18, Pages: 1-8(2019)
- 作者机构：
  
  1.南京中医药大学，南京　 210023；
  2.南京中医药大学　附属医院，南京　 210029
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191524
  CLC： R22; R242; R2-031; R285.5
- Received：23 December 2018，
  
  Published Online：19 April 2019，
  
  Published：20 September 2019
- 稿件说明：
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Fei-xiang LIU, Zi-xuan LIN, Dao-ming XU, et al. Effect of Zuoguiwan in Improving BMD and Trabecular Bone Microarchitecture in Ovariectomy-induced Osteoporosis Rats by Regulating RANKL/OPG Pathway Mediated by β₂AR[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(18): 1-8.
DOI：

Fei-xiang LIU, Zi-xuan LIN, Dao-ming XU, et al. Effect of Zuoguiwan in Improving BMD and Trabecular Bone Microarchitecture in Ovariectomy-induced Osteoporosis Rats by Regulating RANKL/OPG Pathway Mediated by β₂AR[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(18): 1-8. DOI： 10.13422/j.cnki.syfjx.20191524.

摘要

目的：

探讨左归丸治疗绝经后骨质疏松症的分子机制之一是通过对

-肾上腺素能受体(

AR)介导的核转录因子-

B受体激活因子配体(RANKL)/骨保护素(OPG)信号通路的调节。

方法：

通过去卵巢法建立骨质疏松模型，将40只雌性SPF级SD大鼠随机分为模型组、假手术组、雌二醇(50 μg·kg

－1

·d

－1

)组、左归丸低、高剂量(2.3，4.6 g·kg

－1

)组。采用酶联免疫吸附实验检测血清骨转换标志物；显微CT对右侧股骨远端骨密度水平和骨小梁微结构进行测量和分析；实时荧光定量聚合酶链式反应(Real-time PCR)和蛋白免疫印迹法(Western blot)检测胫骨和下丘脑组织中

AR，OPG，RANK mRNA和蛋白表达水平。

结果：

与模型组比较，左归丸可显著降低大鼠血清中Ⅰ型胶原交联羧基端肽(

-CTX)水平(

0.01)，增加骨特异性碱性磷酸酶(BALP)水平(

0.01)，减少卵巢摘除诱导引起的大鼠骨量丢失，改善股骨远端骨小梁显微结构水平。同时，左归丸高、低剂量组均能显著上调胫骨组织中OPG mRNA和蛋白表达(

0.01)，下调下丘脑组织

AR mRNA和蛋白表达水平(

0.01)，同时也能显著下调胫骨组织中RANKL mRNA和蛋白表达水平(

0.01)。

结论：

左归丸改善围绝经期综合症，增加骨量和改善骨小梁显微结构水平的分子机制可能与对

AR介导的RANKL/OPG信号通路的调节有关。

Abstract

Objective:

To investigate the mechanism of Zuoguiwan in treating ovariectomy-induced osteoporosis rats by receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) signaling pathway mediated by

-adrenergic receptor (

AR).

Method:

Forty Sprague-Dawley female rats were randomly divided into Sham-operated group (Sham) and four ovariectomized (OVX) subgroups. Rats in Sham and OVX groups were treated with 17

-estradiol (50 μg·kg

-1

·d

-1

)

and low and high-dose ZGW (2.3

4.6 g·kg

-1

lyophilized powder) for 3 months

respectively. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum markers of bone turnover. Micro-CT was used to evaluate and measure trabecular bone microarchitecture and bone mineral density (BMD) of the right distal femur. Western blot analysis and Real-time PCR were used to measure mRNA and protein expressions of

OPG and RANKL.

Result:

After 12 weeks of treatment with Zuoguiwan

the level of serum

-cross-linked c-telopeptide of type Ι collagen (

-CTX) (

0.01) was lower

while the level of serum bone-specific alkaline phosphatase (BALP) was higher (

0.01) than those in the OVX group. Moreover

it could prevent the OVX-induced bone loss

and alleviate the trabecular bone microarchitecture of distal femur. Furthermore

Zuoguiwan could up-regulate the mRNA and protein expressions of OPG in tibia of the Zuoguiwan groups(

0.01)

reduce the mRNA and protein expressions of

AR in the hypothalamus (

0.01)

and down-regulated the mRNA and protein expressions of RANKL (

0.05) in the tibia

compared with those in the OVX group.

Conclusion:

The mechanism of Zuoguiwan in alleviating BMD and trabecular bone microarchitecture in ovariectomy-induced osteoporosis rats might be related to the regulation of RANKL/OPG Pathway mediated by

AR.

关键词

Keywords

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Effect of Zuoguiwan in Improving BMD and Trabecular Bone Microarchitecture in Ovariectomy-induced Osteoporosis Rats by Regulating RANKL/OPG Pathway Mediated by β2AR

DOI：10.13422/j.cnki.syfjx.20191524

摘要

Abstract

关键词

Keywords

references

Effect of Zuoguiwan in Improving BMD and Trabecular Bone Microarchitecture in Ovariectomy-induced Osteoporosis Rats by Regulating RANKL/OPG Pathway Mediated by β₂AR