Effect and mechanism of Bushen Huanjing Recipe on sarcopenia mice by regulating ferroptosis

Yan HUANG; Sanli XING; Yiran HU; Chuan CHEN

doi:10.16305/j.1007-1334.2022.2107040

您当前的位置：

首页 >

文章列表页 >

Effect and mechanism of Bushen Huanjing Recipe on sarcopenia mice by regulating ferroptosis

更新时间：2022-10-09

- Effect and mechanism of Bushen Huanjing Recipe on sarcopenia mice by regulating ferroptosis
- Shanghai Journal of Traditional Chinese Medicine Vol. 56, Issue 7, Pages: 74-82(2022)
- 作者机构：
  
  1.上海市中医老年医学研究所（上海 200031）
  2.上海中医药大学（上海 201203）
- 作者简介：
- 基金信息：
- DOI：10.16305/j.1007-1334.2022.2107040
  CLC：
扫描看全文
黄研,邢三丽,胡怡然,等.补肾还精方通过调节铁死亡干预小鼠肌少症的效应和机制研究[J].上海中医药杂志,2022,56(7):74-82.

HUANG Yan,XING Sanli,HU Yiran,et al.Effect and mechanism of Bushen Huanjing Recipe on sarcopenia mice by regulating ferroptosis[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(7):74-82.
黄研,邢三丽,胡怡然,等.补肾还精方通过调节铁死亡干预小鼠肌少症的效应和机制研究[J].上海中医药杂志,2022,56(7):74-82. DOI： 10.16305/j.1007-1334.2022.2107040.

HUANG Yan,XING Sanli,HU Yiran,et al.Effect and mechanism of Bushen Huanjing Recipe on sarcopenia mice by regulating ferroptosis[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(7):74-82. DOI： 10.16305/j.1007-1334.2022.2107040.

摘要

目的,2,探讨补肾还精方干预小鼠肌少症的效应和机制。,方法,2,采用老龄快速老化小鼠品系8（SAMP8）小鼠作为肌少症模型，随机分为对照组（0.9%NaCl溶液灌胃组）、补肾组（补肾还精方灌胃组）和Ferr-1组（铁死亡抑制剂Ferrostatin-1腹腔注射组）。补肾组和对照组灌胃干预12周，Ferr-1组干预3周。干预结束后测量小鼠各部分肌肉含量；肌肉测试系统检测小鼠肌肉力量；握力仪检测小鼠抓握力；层粘连蛋白免疫荧光染色检测小鼠肌肉纤维显微结构；检测还原型烟酰胺腺嘌呤二核苷酸磷酸（NAPDH）、谷胱甘肽（GSH）、脂质氧化指标丙二醛（MDA）含量及免疫组化染色检测4-羟基壬烯醛（4-HNE）含量，观察小鼠肌肉组织脂质氧化程度；Western blot检测小鼠肌肉组织中铁死亡调控蛋白Gpx4、SCL7A11、P53及P21的表达情况；透射电镜检测小鼠肌肉纤维线粒体形态。,结果,2,与对照组比较，补肾组、Ferr-1组小鼠各部分肌肉含量提高，肌肉力量和抓握能力提升，肌肉纤维面积增大，肌肉组织脂质过氧化程度降低（,P,<,0.01）。与对照组比较，补肾组、Ferr-1组小鼠肌肉组织铁死亡的两个负相关标志蛋白谷胱甘肽过氧化物酶4（Gpx4）和溶质载体家族7成员11（SLC7A11）的表达显著增加（,P,<,0.001）；而负调控SLC7A11的细胞衰老相关蛋白P53及其下游蛋白P21的表达却显著减少（,P,<,0.001），肌纤维线粒体铁死亡形态改善（,P,<,0.01）。,结论,2,补肾还精方可通过调控肌肉组织铁死亡途径，有效干预治疗小鼠肌少症。

Abstract

Objective,2,To explore the effect and mechanism of Bushen Huanjing Recipe on sarcopenia mice.,Methods,2,The aged senescence accelerated mouse prone 8 （SAMP8） was used as a sarcopenia model， and 36 SAMP8 mice were randomly divided into 0.9%NaCl solution group （control group）， Bushen Huanjing Recipe group （Bushen group） and ferroptosis inhibitor Ferrostatin-1 （Ferr-1） intraperitoneal injection group （Ferr-1 group）. Gavage intervention was given in the control and the Bushen groups for 12 weeks， and inhibitor injection intervention was given for 3 weeks. After the intervention， the muscle mass of the mice was weighed. The muscle strength of the mice was detected by a muscle functional test system， and the maximum grip strength of the mice was detected by a grip strength meter. The microstructure of the mice muscle fibers was detected by the laminin immunofluorescence staining. The contents of reduced nicotinamide adenine dinucleotide phosphate （NAPDH）， glutathione （GSH）， malondialdehyde （MDA） and 4-hydroxynonenal （4-HNE） by immunohistochemistry staining were used to detect lipid oxidation in muscles of the mice. The expression of ferroptosis related proteins such as anti-glutathione peroxidase 4 （Gpx4）， SCL7A11， P53 and P21 in mice muscles was detected by Western blot， and the morphology of mitochondria of muscle fiber in the mice were detected by a transmission electron microscope.,Results,2,Compared with the control group， Bushen Huanjing Recipe and Ferr-1 intervention increased the muscle mass， strength and grip strength as well as the area of muscle fibers in the mice， improved the morphology of mitochondria in muscle fibers（,P,<,0.01）， and reduced lipid peroxidation. The expression of antioxidant glutathione peroxidase （Gpx4） and SLC7A11， the key element of cystine / glutamate antiporter， was significantly increased （,P,<, 0.001）， while the expression of cell senescence-related protein p53 and its downstream protein P21， which negatively regulated SLC7A11， was significantly decreased （,P,<,0.001）.,Conclusion,2,The Bushen Huanjing Recipe can effectively treat sarcopenia in mice by regulating ferroptosis.

关键词

肌少症补肾还精方小鼠模型铁死亡中药研究

Keywords

sarcopeniaBushen Huanjing Recipemice modelferroptosistraditional Chinese herbal medicine research

references

HURLEY B F. Age， gender， and muscular strength［J］. J Gerontol A Biol Sci Med Sci， 1995， 50 （9）： 41-44.

FIELDING R A， VELLAS B， EVANS W J， et al. Sarcopenia： an undiagnosed condition in older adults. Current consensus definition： prevalence， etiology， and consequences. International working group on sarcopenia［J］. J Am Med Dir Assoc， 2011， 12（4）： 249-256.

PASCO J A， WILLIAMS L J， JACKA F N， et al. Sarcopenia and the common mental disorders： a potential regulatory role of skeletal muscle on brain function？［J］. Curr Osteoporos Rep， 2015， 13（5）： 351-357.

MARTINEZ B P， BATISTA A K， GOMES I B， et al. Frequency of sarcopenia and associated factors among hospitalized elderly patients［J］. BMC Musculoskelet Disord， 2015， 16： 108.

HUANG Y， WU B， SHEN D， et al. Ferroptosis in a sarcopenia model of senescence accelerated mouse prone 8 （SAMP8）［J］. Int J Biol Sci， 2021， 17（1）： 151-162.

范利. 老年肌少症与衰弱综合征之间的关系［J］. 中华保健医学杂志，2014， 16（6）： 415-416.

孙帅帅，张立，张泽，等. 从脾肾论治老年肌少症［J］. 中国中医药现代远程教育，2021，19（4）：138-140.

DERAVE W， EIJINDE B O， RAMAEKERS M， et al. Soleus muscles of SAMP8 mice provide an accelerated model of skeletal muscle senescence［J］. Exp Gerontol， 2005， 40（7）： 562-572.

GUO A Y， LEUNG K S， SIU P M， et al. Muscle mass， structural and functional investigations of senescence-accelerated mouse P8 （SAMP8）［J］. Exp Anim， 2015， 64（4）： 425-433.

MENA N P， URRUTIA P J， LOURIDO F， et al. Mitochondrial iron homeostasis and its dysfunctions in neurodegenerative disorders［J］. Mitochondrion， 2015， 21 （3）： 92-105.

DERUISSEAU K C， PARK Y M， DERUISSEAU L R， et al. Aging-related changes in the iron status of skeletal muscle［J］. Exp Gerontol， 2013， 48（11）： 1294-1302.

REARDON T F， ALLEN D G. Iron injections in mice increase skeletalmuscle， iron content， induce oxidative stress and reduce exercise， performance［J］. Exp Physiol， 2009， 94（6）： 720-730.

KASZTURA M， DZIEGALA M， KOBAK K， et al. Both iron excess and iron depletion impair viability of rat H9C2 cardiomyocytes and L6G8C5 myocytes［J］. Kardiol Pol， 2017， 75（3）： 267-275.

ZHAO G. Is iron accumulation a possible risk factor for sarcopenia？［J］. Biol Trace Elem Res， 2018， 186（2）： 379-383.

SCOTT D， BLIZZARD L， FELL J， et al. Associations between dietary nutrient intake and muscle mass and strength in community-dwelling older adults： the tasmanian older adult cohort study［J］. J Am Geriatr Soc， 2010， 58（11）： 2129-2134.

DHILLON R J， HASNI S. Pathogenesis and management of sarcopenia［J］. Clin Geriatr Med， 2017， 33（1）： 17-26.

MARZETTI E， CALVANI R， TOSATO M， et al. Sarcopenia： an overview［J］. Aging Clin Exp Res， 2017， 29（1）： 11-17.

DIXON S J， LEMBERG K M， LAMPRECHT M R， et al. Ferroptosis： an iron-dependent form of nonapoptotic cell death［J］. Cell， 2012， 149（5）： 1060-1072.

LATUNDE-DADA G O. Ferroptosis： role of lipid peroxidation， iron and ferritinophagy［J］. Biochim Biophys Acta Gen Subj， 2017， 1861（8）： 1893-1900.

WEILAND A， WANG Y， WU W， et al. Ferroptosis and its role in diverse brain diseases［J］. Mol Neurobiol， 2019， 56（7）： 4880-4893.

RECALCATI S， GAMMELLA E， CAIRO G. Dysregulation of iron metabolism in cancer stem cells［J］. Free Radic Biol Med， 2019， 133 （3）： 216-220.

Views

606

下载量

CSCD

CNKI被引量

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effects of Xinqian Ganjie Decoction on lncRNA SNHG16， EGFR and MUC5AC mRNA expression in chronic rhinosinusitis mice

Mechanism of Yucan Granules improving podocyte damage and treating diabetic nephropathy

Baicalin modulates gut microbiota and inhibits liver metastasis of colorectal cancer induced by high⁃fat diet

Artemisia annua tea extract attenuating DNCB⁃induced atopic dermatitis by restraining Th2 cell mediated inflammatory responses in BALB/c mice

Mechanism of Huangqi Decoction against liver fibrosis by network pharmacological analysis combined with related cell experiment

Related Author

No data

Related Institution

Department of Otolaryngology， Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Department of Vascular Surgery， Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Department of Nephrology， Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

School of Integrative Medicine， Shanghai University of Traditional Chinese Medicine

Shanghai Key Laboratory of Compound Chinese Medicines， Institute of Chinese Materia Medica， the SATCM Key Laboratory for New Resources & Quality Evaluation of Chinese Medicine， Shanghai University of Traditional Chinese Medicine

⁰