A Network Meta-Analysis of Sarcopenia Characteristic Indicators in Different Mouse Models of Muscular Dystrophy

Abstract

Objective Through a systematic review, compare the differences in characteristic indicators of muscle atrophy in commonly used mouse models, including muscle mass, muscle strength, muscle fiber cross-sectional area, and indicators of atrophy genes such as Murf-1 and Atrogin-1. Qualitatively and quantitatively explore the characteristics of various mouse models of muscle atrophy. Methods A computer search was conducted in databases such as Pubmed, Embase, Cochrane, CNKI, VIP, Wanfang, and Sinomed to collect all literature related to sarcopenia and mouse models, with a search time limit from the establishment of the database to January 17, 2024. The retrieved literature was screened and managed using NoteExpress software, and basic information was summarized using Excel software. Risk of bias assessment was performed using ReviewManange 5.4.1 software, and data analysis was conducted using R software. Results A total of 101 studies involving 1930 mice were included. The modeling methods for sarcopenia included obesity-related (8 studies), tumor-related (10 studies), natural aging (21 studies), dexamethasone-induced (10 studies), hindlimb suspension (7 studies), accelerated aging (6 studies), gene knockout (21 studies), chronic kidney disease-related (3 studies), diabetes-related (9 studies), D-galactose-induced (4 studies), and orchidectomy-induced (2 studies) models. The network meta-analysis results showed that, compared to the normal control group, the top three models in terms of skeletal muscle mass reduction were obesity-related, D-galactose-induced, and accelerated aging models. In terms of muscle strength reduction, the top three models were dexamethasone-induced, hindlimb suspension, and gene knockout models. The cross-sectional area of the gastrocnemius muscle fibers, reflecting the degree of muscle cell atrophy, showed that the top three models in atrophy severity were hindlimb suspension, obesity-related, and tumor-related models. Wet weight of the gastrocnemius muscle, representing muscle mass, was significantly lower in the obesity-related, hindlimb suspension, accelerated aging, gene knockout, chronic kidney disease-related, and diabetes-related models compared to the normal control group (P < 0.05). Grip strength, representing muscle function, was significantly reduced in the obesity-related, tumor-related, natural aging, dexamethasone-induced, hindlimb suspension, accelerated aging, and gene knockout models compared to the normal control group (P < 0.05). HE staining of the gastrocnemius muscle cell cross-sectional area, indicating the degree of muscle cell atrophy, showed significant reductions in the obesity-related, tumor-related, natural aging, dexamethasone-induced, hindlimb suspension, and accelerated aging models compared to the normal control group (P < 0.05). In terms of atrophy gene MuRF-1 expression, the tumor-related and dexamethasone-induced models showed significantly increased expression compared to the normal control group (P < 0.05). For atrophy gene Atrogin-1 expression, the dexamethasone model group showed significantly increased expression compared to the normal control group (P < 0.05). Conclusion Among the 11 sarcopenia models, different models exhibit distinct characteristics in sarcopenia indicators. The obesity-related model is ideal for studying muscle mass reduction, the dexamethasone model is ideal for muscle strength reduction, and the hindlimb suspension model is recommended for skeletal muscle fiber atrophy. The dexamethasone-induced sarcopenia model is recommended for studying the increased expression of atrophy genes MuRF-1 and Atrogin-1. Models showing both skeletal muscle mass and muscle strength reduction include the hindlimb suspension, obesity-related, accelerated aging, and gene knockout models. From the natural aging mouse sarcopenia model, it was found that muscle strength reduction is more sensitive than muscle mass reduction in sarcopenia indicators.