Mechanism of Baoyuan Jiedu Decoction in Alleviating Muscle Atrophy in Apc<sup>min/+</sup> Cachexia Mice

Xin ZONG; Ya-nan ZHANG; Hong-hua ZHANG; Xu-ming JI

doi:10.13422/j.cnki.syfjx.20192102

您当前的位置：

首页 >

文章列表页 >

Mechanism of Baoyuan Jiedu Decoction in Alleviating Muscle Atrophy in Apc^min/+ Cachexia Mice

Pharmacology | 更新时间：2021-02-09

- Mechanism of Baoyuan Jiedu Decoction in Alleviating Muscle Atrophy in Apc^min/+ Cachexia Mice
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 21, Pages: 19-24(2019)
- 作者机构：
  
  1.山东中医药大学，济南　 250355;
  2.浙江中医药大学　基础医学院，杭州　 310053
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20192102
  CLC： R2-0; R22; R285.5; R289
- Received：27 March 2019，
  
  Published Online：18 July 2019，
  
  Published：05 November 2019
- 稿件说明：
移动端阅览
Xin ZONG, Ya-nan ZHANG, Hong-hua ZHANG, et al. Mechanism of Baoyuan Jiedu Decoction in Alleviating Muscle Atrophy in Apc^min/+ Cachexia Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(21): 19-24.
DOI：

Xin ZONG, Ya-nan ZHANG, Hong-hua ZHANG, et al. Mechanism of Baoyuan Jiedu Decoction in Alleviating Muscle Atrophy in Apc^min/+ Cachexia Mice[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(21): 19-24. DOI： 10.13422/j.cnki.syfjx.20192102.

摘要

目的：

研究保元解毒汤对Apc

min/＋

恶病质小鼠血清中白细胞介素-6(IL-6)含量及腓肠肌中肌肉萎缩盒F蛋白1(Atrogin-1)，肌肉特异性环指蛋白-1(MuRF-1)，线粒体解偶联蛋白-2(UCP-2)，解偶联蛋白-3(UCP-3)表达的影响，探讨其改善恶病质模型小鼠肌肉萎缩的作用机制。

方法：

14周龄Apc

min/＋

恶病质小鼠模型，随机分为模型组，保元解毒汤组(23 g·kg

－1

)，甲地孕酮组(0.024 g·kg

－1

)，C57BL/6J小鼠为正常组，每组10只，连续灌胃给药12周，测定腓肠肌质量及肌纤维横径，酶联免疫吸附测定(ELISA)检测Apc

min/＋

恶病质小鼠血清中IL-6含量；蛋白免疫印迹法(Western blot)，实时荧光定量聚合酶链式反应(Real-time PCR)检测小鼠腓肠肌中Atrogin-1，MuRF-1，UCP-2，UCP-3蛋白及mRNA表达。

结果：

与正常组比较，模型组小鼠腓肠肌质量、纤维横径明显减小(

0.05)，血清IL-6含量显著升高，小鼠腓肠肌中Atrogin-1，MuRF-1，UCP-2，UCP-3 mRNA及蛋白表达明显升高(

0.05)；与模型组比较，给药组小鼠腓肠肌质量、腓肠肌纤维横径显著增加，血清中IL-6含量明显降低，腓肠肌中Atrogin-1，MuRF-1，UCP-2，UCP-3 mRNA及蛋白表达明显降低(

0.05)。

结论：

保元解毒汤可改善Apc

min/＋

恶病质小鼠模型肌肉萎缩，其机制可能与降低血清中IL-6含量，下调Atrogin-1，MuRF-1表达，降低线体体UCP-2，UCP-3 mRNA表达相关。

Abstract

Objective:

To study the effect of Baoyuan Jiedu decoction on serum interleukin-6 (IL-6) content

expression of muscle atrophy F-box 1(Atrogin-1)

muscle ring finger-1 (MuRF-1)

uncoupling proteins-2 (UCP-2)

uncoupling proteins-3 (UCP-3) in Apc

min/+

mice

in order to explore the mechanism in improving muscle atrophy in cancer cachexia model.

Method:

The 14-week-old Apc

min/+

cachexia mice model was randomly divided into model group

Baoyuan Jiedu decoction group (23 g·kg

-1

) and megestrol group (0.024 g·kg

-1

). C57BL/6J mice were normal group

with 10 mice in each group

and given continuous intragastric administration for 12 weeks. The quality of gastrocnemius muscle and the transverse diameter of muscle fibers were measured. The content of IL-6 in serum of Apc

min/+

cachexia mice was detected by enzyme-linked immunosorbent assay (ELISA). The expressions of Atrogin-1

MuRF-1

UCP-2

UCP-3 mRNA and protein in gastrocnemius muscle were detected by Western blot and quantitative real-time fluorescence polymerase chain reaction (Real-time PCR).

Result:

Compared with the normal group

the weight of gastrocnemius muscle and the transverse diameter of fibers in the model group decreased significantly (

0.05)

while the concentration of IL-6 in serum and the expressions of Atrogin-1

MuRF-1

UCP-2 and UCP-3 in gastrocnemius muscle of mice increased significantly (

0.05). Compared with the model group

the weight of gastrocnemius muscle

the expression of UCP-3 and protein in the treated group increased significantly (

0.05). The transverse diameter of muscle fibers increased significantly

whereas the concentration of IL-6 in serum and the expressions of Atrogin-1

MuRF-1

UCP-2 and UCP-3 in gastrocnemius muscle of mice decreased significantly (

0.05).

Conclusion:

Reduction of the concentration of IL-6 in serum and the down-regulation of the expressions of Atrogin-1

MuRF-1

UCP-2 and UCP-3 genes may be the possible mechanism of Baoyuan Jiedu decoction in alleviating muscle atrophy in Apc

min/+

cachexia mice model.

关键词

Keywords

references

YANG Q J , ZHAO J R , HAO J , et al . Serum and urine metabolomics study reveals a distinct diagnostic model for cancer cachexia [J]. J Cachexia Sarcopenia Muscle , 2018 , 9 ( 1 ): 71 - 85 .

ZHANG G , LIU Z , DING H , et al . Tumor induces muscle wasting in mice through releasing extracellular Hsp70 and Hsp90 [J]. Nat Commun , 2017 , 8 ( 1 ): 589 .

Aversa Z , Costelli P , Muscaritoli M . Cancer-induced muscle wasting latest findings in prevention and treatment [J]. Ther Adv Med Oncol , 2017 , 9 ( 5 ): 369 - 382 .

洪梓德，莫志贤．中药抗肿瘤机制中的11种信号通路 [J]．中国实验方剂学杂志， 2018 ， 24 ( 21 )： 205 - 218 ．

田龙夫，张琦，王波涛，等．血根碱通过调控PI3K/Akt信号通路诱导胰腺癌细胞凋亡的机制 [J]．中国实验方剂学杂志， 2018 ， 24 ( 19 )： 166 - 171 ．

苗久旺，荆雪宁，高荧，等．自噬对双去甲氧基姜黄素诱导肝癌HepG2细胞凋亡作用的影响 [J]．中国实验方剂学杂志， 2018 ， 24 ( 17 )： 167 - 171 ．

赵能刚，金红艳，刘倩，等．归脾汤制膏治疗晚期癌症恶病质状态的临床观察 [J]．湖北中医药大学学报， 2018 ， 20 ( 5 )： 70 - 72 ．

张媛，罗玲，陶劲．养阴填精化瘀合剂对癌症恶病质患者的临床疗效观察 [J]．南京中医药大学学报， 2018 ， 34 ( 6 )： 561 - 564 ．

章洪华，宗鑫，邓甜甜，等．保元解毒汤通过细胞因子-泛素-蛋白酶体途径干预癌因性肌管萎缩机制的研究 [J]．北京中医药大学学报， 2018 ， 41 ( 8 )： 642 - 647 ．

ZHANG Y , HAN X , OUYANG B , et al . Chinese herbal medicine Baoyuan Jiedu decoction inhibited muscle atrophy of cancer Cachexia through Atrogin-l and MuRF-1 [J]. Evid Based Complement Alternat Med , 2017 , doi: 10.1155/2017/ 6268378 http://doi.org/10.1155/2017/ 6268378 .

Ikeda K , Mutoh M , Teraoka N , et al . Increase of oxidant-related triglycerides and phosphatidylcholines in serum and small intestinal mucosa during development of intestinal polyp formation in Min mice [J]. Cancer Sci , 2011 , 102 ( 1 ): 79 - 87 .

Michael P , Polly N , Karen M , et al . Blood lipids and colorectal polyps: testing an etiologic hypothesis using phenotypic measurements and Mendelian randomization [J]. Cancer Causes Control , 2015 , 26 ( 3 ): 467 - 473 .

王文苹，季旭明，刘超，等．癌性恶病质模型生活质量评价体系的建立及保元解毒汤的干预作用研究 [J]．微循环学杂志， 2012 ， 22 ( 2 )： 91 ．

宗鑫，吴智春，王媛，等．基于中药整合药理学平台分析保元解毒汤干预恶性肿瘤作用机制研究 [J]．中华肿瘤防治杂志， 2018 ， 25 ( 13 )： 931-934，950 ．

于华芸，王文苹，吴智春，等．保元解毒汤对癌性恶病质小鼠骨骼肌蛋白质降解及MAFbx、MuRF-1基因表达的影响 [J]．时珍国医国药， 2015 ， 26 ( 1 )： 226 - 229 ．

CHANG W C L , Jackson C , Riel S , et al . Differential preventive activity of sulindac and atorvastatin in Apc＋/Min-FCCC mice with or without colorectal adenomas [J]. Gut , 2018 , 67 ( 7 ): 1290 - 1298 .

Carson J A , Fix D K , Vanderveen B N . Disrupted skeletal muscle mitochondrial dynamics, mitophagy, and biogenesis during cancer cachexia: a role for inflammation [J]. Oxid Med Cell Longev , 2017 , 15 ( 1 ): 1 - 13 .

CHEN J L , Colgan T D , Walton K L , et al . The TGF-β signalling network in muscle development, adaptation and disease [J]. Adv Exp Med Biol , 2016 , 900 : 97 - 131 .

CHEN L , WANG S , WANG Y , et al . IL-6 influences the polarization of macrophages and the formation and growth of colorectal tumor [J]. Oncotarget , 2018 , 9 ( 25 ): 17443 - 17454 .

Patel H J , Patel B M . TNF-α and cancer cachexia: molecular insights and clinical implications [J]. Life Sci , 2016 , 170 : 56 - 63 .

White J P , Puppa M J , Sato S , et al . IL-6 regulation on skeletal muscle mitochondrial remodeling during cancer cachexia in the ApcMin/＋ mouse [J]. Skeletal Muscle , 2012 , 2 ( 1 ): 14 .

Marchione R , Leibovitch S , Lenormand J L . The translational factor eIF3f: the ambivalent eIF3 subunit [J]. Cell Mol Life Sci , 2013 , 70 ( 19 ): 3603 - 3616 .

YUAN L , HAN J , MENG Q , et al . Muscle-specific E3 ubiquitin ligases are involved in muscle atrophy of cancer cachexia: an in vitro and in vivo study [J]. Oncol Rep , 2015 , 33 ( 5 ): 2261 - 2268 .

Lecker S H , Solomon V , Mitch W E , et al . Muscle protein breakdown and the critical role of the ubiquitin-proteasome pathway in normal and disease states [J]. J Nutr , 1999 , 129 ( 1S ): 227S - 237S .

张洪秀，聂明秀，杨桦，等．泛素蛋白酶体途径及其在肾癌中的研究进展 [J]．昆明理工大学学报：自然科学版， 2015 ， 40 ( 4 )： 84 - 90 ．

Vanderveen B N , Fix D K , Carson J A . Disrupted skeletal muscle mitochondrial dynamics, mitophagy, and biogenesis during cancer cachexia: a role for inflammation [J]. Oxid Med Cell Longev , 2017 , 7 : 1 - 13 .

Bilodeau P A , Coyne E S , Wing S S . The ubiquitin proteasome system in atrophying skeletal muscle: roles and regulation [J]. Am J Physiol Cell Physio , 2016 , 311 ( 3 ): C392 - C403 .

Azzu V , Mookerjee S A , Brand M D . Rapid turnover of mitochondrial uncoupling protein 3 [J]. Biochem J , 2010 , 426 ( 1 ): 13 - 17 .

Sayeed V A , MENG Z , Luciani G , et al . Negative regulation of UCP2 by TGFβ signaling characterizes low and intermediate-grade primary breast cancer [J]. Cell Death Dis , 2010 , 1 ( 7 ): e53 .

Collins S , CAO W , Daniel K W , et al . Adrenoceptors, uncoupling proteins, and energy expenditure [J]. Exp Biol Med , 2001 , 226 ( 11 ): 982 - 990 .

Robbins D , ZHAO Y . New aspects of mitochondrial uncoupling proteins (UCPs) and their roles in tumorigenesis [J]. Int J Mol Sci , 2011 , 12 ( 8 ): 5285 - 5293 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

No data

Related Author

No data

Related Institution

No data

AI问答

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

Mechanism of Baoyuan Jiedu Decoction in Alleviating Muscle Atrophy in Apcmin/+ Cachexia Mice

DOI：10.13422/j.cnki.syfjx.20192102

摘要

Abstract

关键词

Keywords

references

Mechanism of Baoyuan Jiedu Decoction in Alleviating Muscle Atrophy in Apc^min/+ Cachexia Mice