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

您当前的位置：

首页 >

文章列表页 >

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
- Published：20 September 2019，
  
  Published Online：19 April 2019，
  
  Received：23 December 2018，
- 稿件说明：
扫描看全文
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 25(18):1-8(2019)
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 25(18):1-8(2019) 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

左归丸绝经后骨质疏松症核转录因子-κB受体激活因子配体(RANKL)β2-肾上腺素能受体(β2AR)骨保护素(OPG)

Keywords

Zuoguiwanosteoprotegerinreceptor activator of nuclear factor kappa-B ligand(RANKL)β2-adrenergic receptor(β2AR)postmenopausal osteoporosis(OPG)

references

Kendler D L, Geusens P, Zerbini C A F, et al. Teriparatide vs risedronate for osteoporosis-Authors' reply [J].Lancet, 2018, 391(10133): 1896.

Hernlund E, Svedbom A, Ivergård M, et al. Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA) [J].Arch Osteoporos, 2013, 8: 136.

Reid I R. Efficacy, effectiveness and side effects of medications used to prevent fractures [J].J Intern Med, 2015, 277(6): 690-706.

Voss P J, Steybe D, Poxleitner P, et al. Osteonecrosis of the jaw in patients transitioning from bisphosphonates to denosumab treatment for osteoporosis [J].Odontology, 2018, 6(4): 469-480.

张景岳．景岳全书[M]．李继明，王大淳整理．北京：中国中医药出版社，2011：1283-1284．

王如然，鞠大宏，黄胜男，等．左归丸治疗2型糖尿病合并骨质疏松肾阴虚证30例临床观察[J]．中国中医基础医学杂志，2014，20(2)：259-261．

童伟伟．基于补肾益癸理论探讨左归丸防治PMOP的疗效机制[D]．南京：南京中医药大学，2018．

余新莲．左归丸合下瘀血汤治疗原发性骨质疏松症(肾虚血瘀型)临床疗效观察[J]．中医临床研究，2016，8(33)：10-11．

魏志敏．左归丸加减联合钙剂治疗肝肾阴虚型骨质疏松症近期临床疗效分析[D]．成都：成都中医药大学，2015．

谭峰，樊巧玲，卞玉群，等．左、右归丸对去卵巢骨质疏松症大鼠模型骨密度及骨代谢的影响[J]．中国实验方剂学杂志，2015，21(9)：137-140．

LIU F, TAN F, TONG W, et al. Effect of Zuoguiwan on osteoporosis in ovariectomized rats through RANKL/OPG pathway mediated by β2AR [J].Biomed Pharmacoth, 2018, 103: 1052-1060.

吴佳莹，李岳泽，刘红，等．“肾主骨”机理研究—左归丸对Hepcidin、Fpn1及OPG/RANKL mRNA表达的影响[J]．中国中医基础医学杂志，2017，23(11)：1548-1551．

JIANG H, WU Y, Valverde P, et al. Central adiponectin induces trabecular bone mass partly through epigenetic downregulation of cannabinoid receptor CB1 [J].J Cell Physiol, 2019, 234(5): 7062-7069.

Clément-Demange L, Mulcrone P L, Tabarestani T Q, et al. β2ARs stimulation in osteoblasts promotes breast cancer cell adhesion to bone marrow endothelial cells in an IL-1β and selectin-dependent manner [J].J Bone Oncol, 2018, 13: 1-10.

Elefteriou F, Ahn J D, Takeda S, et al. Leptin regulation of bone resorption by the sympathetic nervous system and CART [J].Nature, 2005, 434(7032): 514-520.

Noh H, YU M R, Kim H J, et al. Beta 2-adrenergic receptor agonists are novel regulators of macrophage activation in diabetic renal and cardiovascular complications [J].Kidney Int, 2017, 92(1): 101-113.

MA Y, Nyman J S, TAO H, et al. β2-Adrenergic receptor signaling in osteoblasts contributes to the catabolic effect of glucocorticoids on bone [J].Endocrinology, 2011, 152(4): 1412-1422.

Mohammadpour H, O'Neil R, QIU J, et al. Blockade of host β2-adrenergic receptor enhances graft-versus-tumor effect through modulating APCs [J].J Immunol, 2018, 200(7): 2479-2488.

Lee H, Choue R, Lim H. Effect of soy isoflavones supplement on climacteric symptoms, bone biomarkers, and quality of life in Korean postmenopausal women: a randomized clinical trial [J].Nutr Res Pract, 2017, 11(3): 223-231.

梁文娜，李冠慧，林雪娟，等．二至丸调节Sirt1/Runx2信号通路抑制绝经后骨质疏松症肾阴虚证骨代谢失衡的机制探讨[J]．中华中医药杂志，2018，33(7)：2767-2769．

Johnston B D, Ward W E. The ovariectomized rat as a model for studying alveolar bone loss in postmenopausal women [J].Biomed Res Int, 2015, 2015: 635023.

Parfitt A M, Drezner M K, Glorieux F H, et al. Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee [J].J Bone Miner Res, 2009, 2 (6): 595-610.

Fu P, Gibson C J, Mendes W B, et al. Anxiety, depressive symptoms, and cardiac autonomic function in perimenopausal and postmenopausal women with hot flashes: a brief report [J].Menopause, 2018, 25(12): 1470-1475.

Kruse N T, Hughes W E, Hanada S, et al. Evidence of a greater functional sympatholysis in habitually aerobic trained postmenopausal women [J].J Appl Physiol, 2018, 124(3): 583-591.

Judex S, Pongkitwitoon S. Differential efficacy of 2 vibrating orthodontic devices to alter the cellular response in osteoblasts, fibroblasts, and osteoclasts [J].Dose Response, 2018, 16(3): 1559325818792112.

Akbari Moghaddam Kakhki R, LU Z, Thanabalan A, et al. Eimeria challenge adversely affected long bone attributes linked to increased resorption in 14-day-old broiler chickens [J].Poult Sci, 2019, 98(4): 1615-1621.

ZHANG K, LI B, CHEN Q, et al. Functional calcium binding peptides from pacific cod (gadus macrocephalus) bone: calcium bioavailability enhancing activity and anti-osteoporosis effects in the ovariectomy-induced osteoporosis rat model [J].Nutrients, 2018, 10(9): 1325.

Szulc P, Naylor K, Hoyle N R, et al. Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability [J].Osteoporos Int, 2017, 28 (9): 2541-2556.

Kanis J A, Cooper C, Rizzoli R, et al. Review of the guideline of the American College of Physicians on the treatment of osteoporosis [J].Osteoporos Int, 2018, 29(7): 1505-1510.

Hauk L. Treatment of low BMD and osteoporosis to prevent fractures: updated guideline from the ACP [J].Am Fam Physician, 2018, 97(5): 352-353.

Hanson N A, Bagi C M. Alternative approach to assessment of bone quality using micro-computed tomography [J].Bone, 2004, 35(1): 326-333.

Costa C, Eixarch H, Martínez-Sáez E, et al. Expression of bone morphogenetic proteins in multiple sclerosis lesions [J].Am J Pathol, 2018, 189(3): 665-676.

Mulcrone P L, Campbell J P, Clément-Demange L, et al. Skeletal colonization by breast cancer cells is stimulated by an osteoblast and β2AR-dependent neo-angiogenic switch [J].J Bone Miner Res, 2017, 32(7): 1442-1454.

尚德阳，邓洋洋，孙鑫，等．补肾中药对肾虚骨质疏松症大鼠骨、肾、下丘脑组织中Smurf1/Smurf2的mRNA表达影响[J]．中华中医药杂志，2015，30(10)：3629-3633．

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effect of Decomposed Zuoguiwan Recipes in Improving BMD of Ovariectomized Rats by Regulating OPG/RANKL Pathway Mediated by β₂AR

Zuoguiwan for Treating Congenital Essence Deficiency in Offspring

Zuoguiwan Prevent Decreased Ovarian Reserve in Prenatal Stressed Offspring Rats via TLR4/NF-κB p65 Signaling Pathway

Bioinformatics Reveals Mechanism of Zuoguiwan in Treating Polycystic Ovary Syndrome

Effect of Zuoguiwan on Pancreatic Islet Function in Offspring of Maternal Rats with GDM

Related Author

Ming-yue ZHANG

Feng TAN

Su-min YE

Yi CHAI

Fei-xiang LIU

Cong-ying MAI

Xing LI

Dao-ming XU

Related Institution

School of Basic Medicine,Nanjing University of Chinese Medicine

Affiliated Hospital of Nanjing University of Chinese Medicine

Hubei Provincial Institute of TCM

Hubei Provincial Hospital of TCM

Affiliated Hospital of Hubei University of Chinese Medicine

Postal code：100700
Tel：010-84076882 Email：syfjx_2010@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备11006657号-10 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰

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