清解扶正颗粒通过抑制线粒体依赖的凋亡、激活AMPK-PGC-1α通路缓解5-氟尿嘧啶引起的骨骼肌损伤

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Abstract：Objective Toexplorethetherapeuticmechanismof QingjieFuzheng granules （QFG）forallviating5-fluorouracil （5- FU）-inducedskeletalmuscleatrophy.MethodsMaleBALB/cmicebearingsubcutaneouscolorectalcancerCT26cellxenografts wererandomizedintocontrolgroup，modelgroup，andtreatment group.Themiceinmodelandtreatment groups weregiven intraperitoneal5-Uinjectionsevery3daysandtreatedwithdailygavageofsalineandQFGfor21daysrespectively;emice inthecontrol groupandnormallyfed mice were given onlysalinegavage.Gripping testandhanging testof themice were performedbeforeandafterthetreatment，andonday21，tumorweightandgastrocnemiusmuscleweightweremeasuredand histopathologyandcellapoptosisinthegastrocnemiusmusclewereexaminedwithHEstaining，transmisionelectron microscopyandNELassay.Aotentinthemuscleasmesured，andproteinexpressionsofK，G-Ctc AIF，Apaf-1c-dsseds9eedis The tumor-bearing mice in the control group showed significantly decreased gastrocnemius muscle weight and grip and suspension test scores.Thegastrocnemius muscle showedultrastructure injuries withlowered ATPcontent，obviouscel apoptosis，decreased expressionsofAK， G-1 α， and Bcl-2，ndireased exressiosofa，ytoC，AF，Af-1，c cleaved caspase-3andcleavedcaspase-9.Thesechangeswereobviouslyworsened in5-FU-treated mice，whileQFG treatment significantlyincreasedgastrocnemiusmuscleweightandstrengthameliorateditsultrastructuralinjuries，reducedcell

apoptosis，and reversed theabnormal protein expressions. ConclusionQFGalleviates5-FU-induced skeletalmuscle fatigueintumor-bearingmicebyactivatingtheAMPK/ PGC-1αpathwayand inhibitingmitochondria-dependent apoptosisinthegastrocnemiusmuscle.

Keywords：Qingjiefuzhenggranule;AMP-activated protein kinase; peroxisome proliferator-activated receptor γ coactivator-1α;mitochondrialbiogenesis;skeletalmuscle apoptosis

大肠癌（CRC）是世界上第3大常见癌症，发病率和致死率逐年增加。（剩余17304字）