蛋白质合成在急性肾损伤诱发肌肉萎缩中的作用与机制研究OA

Objective To investigate the role and mechanism of ribosomal DNA(rDNA)transcription and ribo-some biogenesis in muscle atrophy induced by acute kidney injury(AKI).Methods Eight male C57BL/6 mice were randomly divided into a control group(Ctrl)and a model group(AKI).An AKI model was established via in-traperitoneal injection of cisplatin.Muscle atrophy was phenotypically assessed by measuring muscle mass,myofi-ber cross-sectional area(HE staining),and mRNA expression levels of atrophy-related genes(Murf-1,Atrogin-1,Igf-1)using qRT-PCR.In vivo protein synthesis rates were determined via the SUnSET assay(puromycin incorpo-ration).Ribosome biogenesis was evaluated by assessing rRNA content and 47S pre-rRNA expression levels.Myo-tubes differentiated from mouse skeletal muscle cell lines(C2C12 myotubes)were treated with serum from AKI mice,and the effects on rDNA transcription,ribosome biogenesis,and protein metabolism were analyzed using chromatin immunoprecipitation followed by quantitative polymerase chain reaction(ChIP-qPCR)and Western blot.Results AKI successfully induced muscle atrophy,as evidenced by a significant reduction in skeletal muscle mass.The most pronounced decrease occurred in the extensor digitorum longus muscle(21.0%,P<0.01),along with a trend toward reduced myofiber cross-sectional area.At the molecular level,AKI inhibited muscle protein synthesis(83.14%reduction in puromycin incorporation,P<0.000 1)and impaired ribosome bio-genesis,manifested by suppressed rDNA transcription elongation(52.62%decrease in 47S pre-rRNA ITS-1 lev-els,P<0.01)and reduced total rRNA content(65.29%,P<0.000 1).In contrast,serum from AKI mice pro-moted rDNA transcription initiation and protein synthesis in C2C12 myotubes in vitro.Conclusion AKI induces muscle atrophy by suppressing rDNA transcription and ribosome biogenesis in skeletal muscle,leading to impaired protein synthesis.Dysregulated ribosome biogenesis may play a critical role in AKI-induced muscle atrophy.