Mechanism of Jianpi Formula on expression of Akt/FOXO3a pathway in disused muscle atrophy mice

LI Xiaokai; DING Jie; SUN Wen; GAO Sasa; YANG Guangyue; GUO Hailing; ZHAO Yongfang

doi:10.16306/j.1008-861x.2022.05.014

您当前的位置：

首页 >

文章列表页 >

Mechanism of Jianpi Formula on expression of Akt/FOXO3a pathway in disused muscle atrophy mice

Experiment Research | 更新时间：2022-11-01

- Mechanism of Jianpi Formula on expression of Akt/FOXO3a pathway in disused muscle atrophy mice
- Academic Journal of Shanghai University of Traditional Chinese Medicine Vol. 36, Issue 5, Pages: 86-92(2022)
- 作者机构：
  
  1.上海中医药大学附属曙光医院石氏伤科医学中心（上海　201203）
  2.上海市中医药研究院骨伤科研究所（上海　201203）
- 作者简介：
- 基金信息：
- DOI：10.16306/j.1008-861x.2022.05.014
  CLC：
扫描看全文
李小凯,丁劼,孙雯等.健脾方对废用性肌肉萎缩小鼠Akt/FOXO3a通路表达的机制研究[J].上海中医药大学学报,2022,36(05):86-92.

LI Xiaokai,DING Jie,SUN Wen,et al.Mechanism of Jianpi Formula on expression of Akt/FOXO3a pathway in disused muscle atrophy mice[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2022,36(05):86-92.
李小凯,丁劼,孙雯等.健脾方对废用性肌肉萎缩小鼠Akt/FOXO3a通路表达的机制研究[J].上海中医药大学学报,2022,36(05):86-92. DOI： 10.16306/j.1008-861x.2022.05.014.

LI Xiaokai,DING Jie,SUN Wen,et al.Mechanism of Jianpi Formula on expression of Akt/FOXO3a pathway in disused muscle atrophy mice[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2022,36(05):86-92. DOI： 10.16306/j.1008-861x.2022.05.014.

摘要

目的,2,探究健脾方基于Akt/FOXO3a信号通路预防小鼠废用性肌肉萎缩的作用机制。,方法,2,将45只10周龄雄性C57/BL6小鼠随机分为对照组、模型组及健脾方组。通过后肢卸载构建废用性肌肉萎缩小鼠模型。对照组和模型组小鼠每天每只灌胃给予0.2 ml 0.9% NaCl溶液，健脾方组小鼠每天每只灌胃给予0.2 ml健脾方混悬液。给药28 d后，称取小鼠体质量、肌肉湿重（累积肌肉、腓肠肌、比目鱼肌、胫骨前肌、趾长伸肌及股四头肌），qRT-PCR检测腓肠肌中,IGF-1、PI3K、Akt、Atrogin,及,MuRF1 ,mRNA的表达水平，Western blot检测腓肠肌中p-Akt、p-FOXO3a、Akt、FOXO3a蛋白的表达水平。,结果,2,①与对照组比较，模型组小鼠四肢抓力/体质量比值、肌肉湿重/体质量比值、肌纤维横截面积和直径明显降低（,P,<,0.05）。与模型组比较，健脾方组小鼠四肢抓力/体质量比值明显增加（,P,<,0.05）；累积肌肉、比目鱼肌、胫骨前肌、股四头肌的湿重/体质量比值明显增加（,P,<,0.05）；肌纤维横截面积明显增加（,P,<,0.05）。②健脾方干预后，小鼠腓肠肌,IGF-1、Akt, mRNA表达明显增加（,P,<,0.05），,Atrogin、MuRF1, mRNA表达明显减少（,P,<,0.05）；p-Akt蛋白表达升高，p-FOXO3a蛋白表达降低。,结论,2,健脾方可能通过上调Akt磷酸化水平抑制Akt/FOXO3a信号通路来预防废用性肌肉萎缩。

Abstract

Objective： To explore the mechanism of Jianpi Formula in preventing disuse muscle atrophy in mice based on Akt/FOXO3a signaling pathway.,Methods,2,Forty-five male C57/BL6 mice were randomly divided into control group， model group and Jianpi Formula group. Disuse muscular atrophy mouse model was established by hindlimb unloading. Mice in control group and model group were given 0.2 ml 0.9% NaCl solution by gavage every day， and mice in Jianpi Formula group were given 0.2 ml Jianpi Formula suspension by gavage every day. After 28 d of drug administration， the body weight and wet muscle weight （accumulation of muscle， gastrocnemius muscle， soleus muscle， tibialis anterior muscle， extensor digitorum longus muscle and quadriceps femoris muscle） of mice were weighed. Moreover， qRT-PCR was used to detect, IGF-1， PI3K， Akt,， ,Atrogin, and ,MuRF1, mRNA expression level， Western blot was used to detect p-Akt， p-FOXO3a， Akt and FOXO3a protein expression level in gastrocnemius muscle.,Results,2,①Compared with the control group， the grip strength/body weight ratio， wet weight/body weight ratio of muscles， cross-sectional area and diameter of muscle fiber in mice of the model group significantly decreased （,P,<,0.05）. Compared with the model group， the grip strength/body weight ratio significantly increased （,P,<,0.05）； the wet weight/body weight ratio of cumulative muscle， soleus muscle， tibialis anterior muscle and quadriceps femoris muscle significantly increased （,P,<,0.05）； muscle fiber cross-sectional area significantly increased （,P,<,0.05）. ②After the intervention of Jianpi Formula， ,IGF-1, and ,Akt, mRNA expression significantly increased （,P,<,0.05） in gastrocnemius muscle of mice， while ,Atrogin, and ,MuRF1, mRNA expression significantly decreased （,P,<,0.05）； p-Akt protein expression increased， p-FOXO3a protein expression decreased.,Conclusion,2,Jianpi Formula may be prevent disuse muscular atrophy by inhibiting Akt/FOXO3a signaling pathway through up-regulating Akt phosphorylation.

关键词

健脾方废用性肌萎缩后肢卸载抓力腓肠肌Akt/FOXO3a信号通路

Keywords

Jianpi Formuladisuse muscle atrophyhindlimb unloadinggrip strengthgastrocnemius muscleAkt/FOXO3a signaling pathway

references

GLASS D J. Molecular mechanisms modulating muscle mass［J］. Trends Mol Med， 2003， 9（8）： 344-350.

CRUZ-JENTOFT A J，BAHAT G，BAUER J，et al. Sarcopenia：revised European consensus on definition and diagnosis［J］. Age Ageing， 2019， 48（1）： 16-31.

王立童，赵咏芳，王翔，等. 密骨胶囊和健脾方对切卵大鼠小肠及腓肠肌中VDR mRNA表达的影响［J］. 中国骨伤，2009， 22（5）： 367-370.

GLASS D J. Skeletal muscle hypertrophy and atrophy signaling pathways［J］. Int J Biochem Cell Biol，2005， 37（10）： 1974-1984.

GLASS D J. PI3 kinase regulation of skeletal muscle hypertrophy and atrophy［J］. Curr Top Microbiol Immunol， 2010， 346： 267-278.

SANDRI M. Signaling in muscle atrophy and hypertrophy［J］. Physiology （Bethesda）， 2008， 23： 160-170.

TAKEMOTO R，SEJIMA T，HAN L K，et al. Disuse muscle atrophy-improving effect of ninjin’yoeito in a mouse model［J］. Neuropeptides， 2021， 90： 102199.

WANG D，CHEN J， LIU X， et al. Retraction Note： A Chinese herbal formula，Jian-Pi-Yi-Shen decoction，improves muscle atrophy via regulating mitochondrial quality control process in 5/6 nephrectomised rats［J］. Sci Rep， 2021， 11（1）： 12831.

ZHOU L，HUANG Y F，XIE H，et al. Herbal complex “Buyang Huanwu Tang” improves motor endplate function of denervated-dependent skeletal muscle atrophy in rat［J］. J Integr Neurosci，2020， 19（1）： 89-99.

BOWEN T S， SCHULER G， ADAMS V. Skeletal muscle wasting in cachexia and sarcopenia：molecular pathophysiology and impact of exercise training［J］. J Cachexia Sarcopenia Muscle， 2015， 6（3）： 197-207.

KANG S， LEE H， KIM M， et al. Forkhead box O3 plays a role in skeletal muscle atrophy through expression of E3 ubiquitin ligases MuRF-1 and atrogin-1 in Cushing’s syndrome［J］. Am J Physiol Endocrinol Metab， 2017， 312（6）： E495-E507.

MILAN G， ROMANELLO V， PESCATORE F， et al. Regulation of autophagy and the ubiquitin-proteasome system by the FoxO transcriptional network during muscle atrophy［J］. Nat Commun，2015， 6： 6670.

WENDT A，THOMPSON V F，GOLL D E. Interaction of calpastatin with calpain：a review［J］. Biol Chem， 2004， 385（6）： 465-472.

ZHANG S F， ZHANG Y， LI B， et al. Physical inactivity induces the atrophy of skeletal muscle of rats through activating AMPK/FoxO3 signal pathway［J］. Eur Rev Med Pharmacol Sci， 2018， 22（1）： 199-209.

BROCCA L， TONIOLO L， REGGIANI C， et al. FoxO-dependent atrogenes vary among catabolic conditions and play a key role in muscle atrophy induced by hindlimb suspension［J］. J Physiol，2017， 595（4）： 1143-1158.

GARCIA-PRAT L， PERDIGUERO E， ALONSO-MARTIN S，et al. FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age［J］. Nat Cell Biol， 2020， 22（11）： 1307-1318.

RUBIO B，MORA C，PINTADO C，et al. The nutrient sensing pathways FoxO1/3 and mTOR in the heart are coordinately regulated by central leptin through PPARbeta/delta. Implications in cardiac remodeling［J］. Metabolism， 2021， 115： 154453.

BARCLAY R D，BURD N A，TYLER C，et al.The Role of the IGF-1 Signaling Cascade in Muscle Protein Synthesis and Anabolic Resistance in Aging Skeletal Muscle［J］. Front Nutr， 2019， 6： 146.

Views

400

下载量

CSCD

CNKI被引量

Alert me when the article has been cited

提交

Tools

Publicity Resources

No data

Related Author

No data

Related Institution

No data

⁰