Levels of Relevant Inflammatory Factors and Oxidative Stress Markers in Alcoholic Myopathy: a Meta-analysis

doi:10.12114/j.issn.1007-9572.2022.0214

Abstract

Abstract:

Background

Alcoholism can lead to alcoholic myopathy. Although there are over ten biomarkers used to evaluate this disease, their diagnostic value remains controversial.

Objective

To systematically evaluate the effects of alcoholic myopathy on levels of relevant inflammatory factors and oxidative stress markers.

Methods

The VIP Database for Chinese Technical Periodicals, Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure, Web of Science, PubMed, Embase and Cochrane Library databases were searched for animal intervention studies on inflammatory factors and oxidative stress markers in alcoholic myopathy from February 1, 1990 to August 31, 2021 to retrieve. RevMan 5.4.1 was used for Meta-analysis. Outcome measures included reduced glutathione (GSH) and malondialdehyde (MDA) levels as well as the mRNA expression levels of insulin-like growth factor 1 (IGF-1) and interleukin 6 (IL-6) .

Results

Ultimately, 17 animal interventionstudies were included, and the results of Meta-analysis showed that the levels of IGF-1 mRNA expression〔SMD=-3.09, 95%CI (-5.75, -0.43) , P=0.02〕and GSH levels〔SMD=-4.20, 95%CI (-6.24, -2.17) , P<0.000 01〕in the experimental group were lower than those in the control group. The levels of IL-6 mRNA expression〔SMD=3.75, 95%CI (2.93, 4.57) , P<0.000 01〕and MDA levels〔SMD=0.97, 95%CI (0.64, 1.29) , P<0.000 01〕were higher in the experimental group than those in the control group.

Conclusion

Animals with alcoholic myopathy show decreased IGF-1 mRNA expression and GSH levels but increased IL-6 mRNA expression and MDA levels.

Key words: Myopathy, Chronic alcoholic myopathy, Oxidative stress, Inflammatory factor infiltration, Systematic evaluation, Meta analysis

摘要：

背景

酒精中毒会引发酒精性肌病。目前，评价酒精性肌病的标志物有10种以上，但这些标志物的评价价值尚存争议。

目的

系统评价酒精性肌病相关炎性因子和氧化应激标志物水平的影响。

方法

检索维普网（VIP）、万方数据知识服务平台（Wanfang Data）、中国知网（CNKI）、Web of Science、PubMed、Embase、Cochrane Library等数据库，筛选关于酒精性肌病相关炎性因子和氧化应激标志物的动物干预研究，检索时间为1990-02-01至2021-08-31。采用RevMan 5.4.1进行Meta分析。结局指标包括还原型谷胱甘肽（GSH）、丙二醛（MDA）、胰岛素样生长因子1（IGF-1）及白介素6（IL-6）mRNA表达水平。

结果

最终纳入17项动物干预试验，Meta分析结果表明，试验组IGF-1 mRNA表达水平〔SMD=-3.09，95%CI（-5.75，-0.43），P=0.02〕和GSH水平〔SMD=-4.20，95%CI（-6.24，-2.17），P<0.000 01〕低于对照组；试验组IL-6 mRNA表达水平〔SMD=3.75，95%CI（2.93，4.57），P<0.000 01〕和MDA水平〔SMD=0.97，95%CI（0.64，1.29），P<0.000 01〕高于对照组。

结论

发生酒精性肌病时IGF-1 mRNA表达水平和GSH水平降低，IL-6 mRNA表达水平和MDA水平升高。

关键词: 肌病, 慢性酒精性肌病, 氧化应激, 炎性因子浸润, 系统评价, Meta分析

WANG Nan,Motuziuk OLEKSANDR,Mishchenko IRYNA, et al. Levels of Relevant Inflammatory Factors and Oxidative Stress Markers in Alcoholic Myopathy: a Meta-analysis[J]. Chinese General Practice, 2022, 25(33): 4123-4129. DOI: 10.12114/j.issn.1007-9572.2022.0214.
汪楠,Motuziuk OLEKSANDR,Mishchenko IRYNA等. 酒精性肌病相关炎性因子和氧化应激标志物水平的Meta分析[J]. 中国全科医学, 2022, 25(33): 4123-4129. DOI: 10.12114/j.issn.1007-9572.2022.0214.

Figures/Tables 9

References 35

[1]	JAYASEKARA H, ENGLISH D R, ROOM R，et al. Alcohol consumption over time and risk of death：a systematic review and meta-analysis[J]. Am J Epidemiol，2014，179(9):1049-1059. DOI：10.1093/aje/kwu028.
[2]	GRISWOLD M G, FULLMAN N, HAWLEY C，et al. Alcohol use and burden for 195 countries and territories，1990-2016：a systematic analysis for the Global Burden of Disease Study 2016[J]. The Lancet，2018，392(10152):1015-1035. DOI：10.1016/S0140-6736(18)31310-2.
[3]	MILLWOOD I Y, WALTERS R G, MEI X W，et al. Conventional and genetic evidence on alcohol and vascular disease aetiology：a prospective study of 500 000 men and women in China[J]. Lancet，2019，393(10183):1831-1842. DOI：10.1016/S0140-6736(18)31772-0.
[4]	PREEDY V R, ADACHI J, UENO Y，et al. Alcoholic skeletal muscle myopathy：definitions，features，contribution of neuropathy，impact and diagnosis[J]. Eur J Neurol，2001，8(6):677-687. DOI：10.1046/j.1468-1331.2001.00303.x.
[5]	BRAZEAU G A, AL-SUWAYEH S, PERIS J，et al. Creatine kinase release from isolated EDL muscles in chronic ethanol-treated rats[J]. Alcohol，1995，12(2):145-149. DOI：10.1016/0741-8329(94)00074-3.
[6]	COOK E B, ADEBIYI L A, PREEDY V R，et al. Chronic effects of ethanol on muscle metabolism in the rat[J]. Biochim Biophys Acta，1992，1180(2):207-214. DOI：10.1016/0925-4439(92)90070-4.
[7]	GARRIGA J, FERNÁNDEZ-SOLÁ J, ADANERO E，et al. Metabolic effects of ethanol on primary cell cultures of rat skeletal muscle[J]. Alcohol，2005，35(1):75-82. DOI：10.1016/j.alcohol.2004.12.003.
[8]	CROWELL K T, LAUFENBERG L J, LANG C H. Chronic alcohol consumption，but not acute intoxication，decreases in vitro skeletal muscle contractile function[J]. Alcohol Clin Exp Res，2019，43(10):2090-2099. DOI：10.1111/acer.14179.
[9]	DURÁN CASTELLÓN M C, GONZÁLEZ-REIMERS E, LÓPEZ-LIROLA A，et al. Alcoholic myopathy：lack of effect of zinc supplementation[J]. Food Chem Toxicol，2005，43(9):1333-1343. DOI：10.1016/j.fct.2005.03.006.
[10]	CLARY C R, GUIDOT D M, BRATINA M A，et al. Chronic alcohol ingestion exacerbates skeletal muscle myopathy in HIV-1 transgenic rats[J]. AIDS Res Ther，2011，8:30. DOI：10.1186/1742-6405-8-30.
[11]	DEKEYSER G J, CLARY C R, OTIS J S. Chronic alcohol ingestion delays skeletal muscle regeneration following injury[J]. Regen Med Res，2013，1(1):2. DOI：10.1186/2050-490X-1-2.
[12]	ADAMS C, CONIGRAVE J H, LEWOHL J，et al. Alcohol use disorder and circulating cytokines：a systematic review and meta-analysis[J]. Brain Behav Immun，2020，89:501-512. DOI：10.1016/j.bbi.2020.08.002.
[13]	MA L L, WANG Y Y, YANG Z H，et al. Methodological quality （risk of bias） assessment tools for primary and secondary medical studies：what are they and which is better?[J]. Mil Med Res，2020，7(1):7. DOI：10.1186/s40779-020-00238-8.
[14]	LANG C H, FROST R A, KUMAR V，et al. Impaired protein synthesis induced by acute alcohol intoxication is associated with changes in eIF4E in muscle and eIF2B in liver[J]. Alcohol Clin Exp Res，2000，24(3):322-331.
[15]	LANG C H, FROST R A, SVANBERG E，et al. IGF-I/IGFBP-3 ameliorates alterations in protein synthesis，eIF4E availability，and myostatin in alcohol-fed rats[J]. Am J Physiol Endocrinol Metab，2004，286(6):E916-926. DOI：10.1152/ajpendo.00554.2003.
[16]	OTIS J S, BROWN L A S, GUIDOT D M. Oxidant-induced atrogin-1 and transforming growth factor-beta1 precede alcohol-related myopathy in rats[J]. Muscle Nerve，2007，36(6):842-848. DOI：10.1002/mus.20883.
[17]	OTIS J S, GUIDOT D M. Procysteine stimulates expression of key anabolic factors and reduces plantaris atrophy in alcohol-fed rats[J]. Alcohol Clin Exp Res，2009，33(8):1450-1459. DOI：10.1111/j.1530-0277.2009.00975.x.
[18]	WANG J F, CHU H Y, ZHAO H，et al. Nitricoxide synthase-induced oxidative stress in prolonged alcoholic myopathies of rats[J]. Mol Cell Biochem，2007，304(1/2):135-142. DOI：10.1007/s11010-007-9494-6.
[19]	初海鹰，王昊，王剑锋，等. 银杏叶提取物对酒精所致大鼠骨骼肌损伤的保护和治疗的作用[J]. 解剖科学进展，2010，16(1):66-70. DOI：10.16695/j.cnki.1006-2947.2010.01.007.
[20]	GONZÁLEZ-REIMERS E, DURÁN-CASTELLÓN M C, LÓPEZ-LIROLA A，et al. Alcoholic myopathy：vitamin D deficiency is related to muscle fibre atrophy in a murine model[J]. Alcohol and Alcoholism，2010，45(3):223-230. DOI：10.1093/alcalc/agq010.
[21]	KORZICK D H, SHARDA D R, PRUZNAK A M，et al. Aging accentuates alcohol-induced decrease in protein synthesis in gastrocnemius[J]. Am J Physiol Regul Integr Comp Physiol，2013，304(10):R887-898. DOI：10.1152/ajpregu.00083.2013.
[22]	MOLINA P E, LANG C H, MCNURLAN M，et al. Chronic alcohol accentuates simian acquired immunodeficiency syndrome-associated wasting[J]. Alcohol Clin Exp Res，2008，32(1):138-147. DOI：10.1111/j.1530-0277.2007.00549.x.
[23]	RUDEANU M, MURESAN A, TACHE S，et al. Moderate alcohol consumption and the oxidants/antioxidants imblance in rats[J]. Fiziologia-Physiology，2008，18:7-10.
[24]	NGUYEN V A, LE T, TONG M，et al. Impaired insulin/IGF signaling in experimental alcohol-related myopathy[J]. Nutrients，2012，4(8):1058-1075. DOI：10.3390/nu4081058.
[25]	WORRALL S, NIEMELA O, PARKKILA S，et al. Protein adducts in type I and type Ⅱ fibre predominant muscles of the ethanol-fed rat：preferential localisation in the sarcolemmal and subsarcolemmal region[J]. Eur J Clin Invest，2001，31(8):723-730. DOI：10.1046/j.1365-2362.2001.00848.x.
[26]	PATEL V B, WORRALL S, EMERY P W，et al. Protein adduct species in muscle and liver of rats following acute ethanol administration[J]. Alcohol Alcohol，2005，40(6):485-493. DOI：10.1093/alcalc/agh196.
[27]	OTIS J S, GUIDOT D M. Procysteine increases alcohol-depleted glutathione stores in rat plantaris following a period of abstinence[J]. Alcohol Alcohol，2010，45(6):495-500. DOI：10.1093/alcalc/agq066.
[28]	STEINER J L, LANG C H. Dysregulation of skeletal muscle protein metabolism by alcohol[J]. Am J Physiol Endocrinol Metab，2015，308(9):E699-712. DOI：10.1152/ajpendo.00006.2015.
[29]	ESTRUCH R, NICOLÁS J M, VILLEGAS E，et al. Relationship between ethanol-related diseases and nutritional status in chronically alcoholic men[J]. Alcohol and Alcoholism，1993，28(5):543-550. DOI：10.1016/0741-8329(93)90031-I.
[30]	SHENKMAN B S, ZINOVYEVA O E, BELOVA S P，et al. Cellular and molecular signatures of alcohol-induced myopathy in women[J]. Am J Physiol Endocrinol Metab，2019，316(5):E967-976. DOI：10.1152/ajpendo.00513.2018.
[31]	BORRISSER-PAIRÓ F, ANTÚNEZ E, TOBÍAS E，et al. Insulin-like growth factor 1 myocardial expression decreases in chronic alcohol consumption[J]. Regen Med Res，2013，1(1):3. DOI：10.1186/2050-490X-1-3.
[32]	HUANG M C, CHEN C H, PENG F C，et al. Alterations in oxidative stress status during early alcohol withdrawal in alcoholic patients[J]. Taiwan Yi Zhi，2009，108(7):560-569. DOI：10.1016/S0929-6646(09)60374-0.
[33]	MANZO-AVALOS S, SAAVEDRA-MOLINA A. Cellular and mitochondrial effects of alcohol consumption[J]. Int J Environ Res Public Health，2010，7(12):4281-4304. DOI：10.3390/ijerph7124281.
[34]	GONZÁLEZ-REIMERS E, FERNÁNDEZ-RODRÍGUEZ C M, SANTOLARIA-FERNÁNDEZ F，et al. Interleukin-15 and other myokines in chronic alcoholics[J]. Alcohol Alcohol，2011，46(5):529-533. DOI：10.1093/alcalc/agr064.
[35]	YANG H, HUA J L, WANG C. Anti-oxidation and anti-aging activity of polysaccharide from Malus micromalus Makino fruit wine[J]. Int J Biol Macromol，2019，121:1203-1212. DOI：10.1016/j.ijbiomac.2018.10.096.

第一作者	发表时间（年）	实验鼠类型	分组方式	样本量（只）		建模方式		饲养时间	取材部位	结局指标
第一作者	发表时间（年）	实验鼠类型	分组方式	实验组	对照组	实验组	对照组	饲养时间	取材部位	结局指标
CASTELLÓN^[9]	2005	SD大鼠	—	10	10	36%酒精琼脂饲养	常规饲养	5周	腓肠肌	①②
CLARY^[10]	2011	大鼠	随机	6	6	36%酒精流食饲养	常规饲养	12周	跖肌	③④
DEKEYSER^[11]	2013	C57Bl/6小鼠	—	5	5	20%酒精流食饲养	常规饲养	18~20周	骨骼肌	③④
LANG^[14]	2000	SD大鼠	—	8	8	75 mmol/kg酒精腹腔注射	常规饲养	2.5 h	腓肠肌	①
LANG^[15]	2004	SD大鼠	—	8	8	30%酒精琼脂饲养	常规饲养	16周	腓肠肌	①
OTIS^[16]	2007	SD大鼠	—	6	6	36%酒精流食饲养	常规饲养	6周或28周	跖肌	④
OTIS^[17]	2009	SD大鼠	—	7	7	36%酒精流食饲养	常规饲养	35周	跖肌	④③①
WANG^[18]	2007	SD大鼠	—	12	38	56%酒精流食饲养	常规饲养	10周	跖肌/比目鱼肌	④②
初海鹰^[19]	2010	SD大鼠	—	20	10	56%酒精流食饲养	常规饲养	11周	跖肌	②④
GONZÁLEZ-REIMERS^[20]	2010	SD大鼠	—	10	10	36%酒精流食饲养	常规饲养	5周	腓肠肌	②
KORZICK^[21]	2013	Fischer 344大鼠	随机	9	9	37%酒精流食饲养	常规饲养	20周	腓肠肌	①③
MOLINA^[22]	2008	大鼠	随机	13	13	30%酒精流食饲养	常规饲养	12周	骨骼肌	①③
RUDEANU^[23]	2008	大鼠	—	10	10	20%酒精流食饲养	常规饲养	4周	骨骼肌	②
NGUYEN^[24]	2012	SD大鼠	—	13	13	35%酒精流食饲养	常规饲养	8周	腓肠肌	①
WORRALL^[25]	2001	Wistar大鼠	—	6	6	36%酒精流食饲养	常规饲养	6周	比目鱼肌	②
PATEL^[26]	2005	Wistar大鼠	—	8	8	75 mmol/kg酒精腹腔注射	常规饲养	2.5 h	腓肠肌	②
GUIDOT^[27]	2010	SD大鼠	随机	7	7	36%酒精流食饲养	常规饲养	12周	腓肠肌	④

第一作者	发表时间（年）	实验鼠类型	分组方式	样本量（只）		建模方式		饲养时间	取材部位	结局指标
第一作者	发表时间（年）	实验鼠类型	分组方式	实验组	对照组	实验组	对照组	饲养时间	取材部位	结局指标
CASTELLÓN^[9]	2005	SD大鼠	—	10	10	36%酒精琼脂饲养	常规饲养	5周	腓肠肌	①②
CLARY^[10]	2011	大鼠	随机	6	6	36%酒精流食饲养	常规饲养	12周	跖肌	③④
DEKEYSER^[11]	2013	C57Bl/6小鼠	—	5	5	20%酒精流食饲养	常规饲养	18~20周	骨骼肌	③④
LANG^[14]	2000	SD大鼠	—	8	8	75 mmol/kg酒精腹腔注射	常规饲养	2.5 h	腓肠肌	①
LANG^[15]	2004	SD大鼠	—	8	8	30%酒精琼脂饲养	常规饲养	16周	腓肠肌	①
OTIS^[16]	2007	SD大鼠	—	6	6	36%酒精流食饲养	常规饲养	6周或28周	跖肌	④
OTIS^[17]	2009	SD大鼠	—	7	7	36%酒精流食饲养	常规饲养	35周	跖肌	④③①
WANG^[18]	2007	SD大鼠	—	12	38	56%酒精流食饲养	常规饲养	10周	跖肌/比目鱼肌	④②
初海鹰^[19]	2010	SD大鼠	—	20	10	56%酒精流食饲养	常规饲养	11周	跖肌	②④
GONZÁLEZ-REIMERS^[20]	2010	SD大鼠	—	10	10	36%酒精流食饲养	常规饲养	5周	腓肠肌	②
KORZICK^[21]	2013	Fischer 344大鼠	随机	9	9	37%酒精流食饲养	常规饲养	20周	腓肠肌	①③
MOLINA^[22]	2008	大鼠	随机	13	13	30%酒精流食饲养	常规饲养	12周	骨骼肌	①③
RUDEANU^[23]	2008	大鼠	—	10	10	20%酒精流食饲养	常规饲养	4周	骨骼肌	②
NGUYEN^[24]	2012	SD大鼠	—	13	13	35%酒精流食饲养	常规饲养	8周	腓肠肌	①
WORRALL^[25]	2001	Wistar大鼠	—	6	6	36%酒精流食饲养	常规饲养	6周	比目鱼肌	②
PATEL^[26]	2005	Wistar大鼠	—	8	8	75 mmol/kg酒精腹腔注射	常规饲养	2.5 h	腓肠肌	②
GUIDOT^[27]	2010	SD大鼠	随机	7	7	36%酒精流食饲养	常规饲养	12周	腓肠肌	④