PRMT7在Duchenne肌营养不良小鼠肌肉炎症、氧化应激和纤维化中的作用及机制研究

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【中图分类号】R746.2【文献标志码】A【收稿日期】2024-01-26

【Abstract】Objective：Toinvestigatetheroleandmchanismofproteinargininemethyltransferase7（PRMT）inmuscleinflammation，oxidativestres，ndrosisinDucheeusculardstropyice.Metods：Inthisudy，7BL/6ild-temicered as thecontrolgroup，mdxmice as themodelgroupofDuchennemusculardystrophy，and mdxmice injectedwithAAV9-PRM7bythe caudalveinastheexperimental group.Thelevelsofinflammatoryfactorsweremeasuredbyanenzyme-linkedimmunosorbentaay. Oxidativestress-relatedindicators weremeasuredusingcommercialkits.Massonstainingwasprfored toassessthefibrosis degree of the gastrocnemius.The expresionofPRMT7，peroxisome proliferator-activatedreceptor gammacoactivator-1alpha（PGC- Π1α ），and nuclearfactorerythroid2-relatedfactor2（Nrf2）wasanalyzedbyaWesternblotassay.Thearginine methylationlevelof PGC- l∝ was determinedbyanimmunoprecipitationassy.Results：PRMT7expressionwassignificantlyeducedinthegastrocnemiusofdxmice （0.67±0.03，F=70.764，P=0.001） .The up-regulation of PRMT7 resulted in significant decreases in the levels of inflammatory factors （interleukin-1β： 167.87±13.25 ， F =407.751， P <0.001；tumor necrosis factor- F =55.996， P =0.048）andsignificantimprovements in the oxidative stress and fibrosis status in the gastrocnemius of mdx mice（reactive oxygen species： 1.16±0.03，F= （20 86.820，P=O.0o8;malondialdehyde： 66.11±3.84 ，F=228.175， P= 0.001;glutathione/oxidized glutathione： 2.53±0.06 ，F=499.962，P< 0.001；fibrosis area： 10.33±0.47 ， F =604.272， P =0.002），an increasein thearginine methylationlevel ofPGC- ⋅1α ，and significant increases in proteinlevels of PGC-1α and Nrf2（PGC-1α：1.94± 0.11，F=31.565 ，P=0.038;Nrf2：1.53±0.12，F=140.761，P<0.001）. Conclusion：Increasing PRMT7 expression attenuates the inflammation，xidativestressndpathologicalsateofrosisinthegastrocnesofdxmice.sesfectsaybeaceedtoghte PGC-1α/Nrf2 pathway.

【Key wordsmusculardtrophy;proteinarginineetyltransferase7iflammatio;rosis;peroxisomeproliferatoctivatedreeptorgammacoactivator-1alpha;nuclear factor erythroid 2-related factor2

Duchenne 肌营养不良（duchenne muscular dys-trophy，DMD）是一种严重的、进行性的肌肉萎缩疾病，由抗肌萎缩蛋白缺失引起。（剩余11274字）