Experimental Study on the Effects of Ghrelin on Gastric Smooth Muscle and Posterior Limb Skeletal Muscle in Mice

Ping Wang¹Cunbo Yu¹Yibing Li^2,3Xiaoxiao Zhang^2,3Xueli Yao¹Yingjian Zhang^2,3*

• ¹College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang, Henan Province, China
• ²Department of Gastroenterology,The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan Province, China
• ³Henan Medical Key Laboratory of Gastrointestinal Microecology and Hepatology, Luoyang, Henan Province, China

The study aims to systematically explore the regulatory effects of ghrelin on the hindlimb skeletal muscle and gastrointestinal smooth muscle in mice, providing innovative theoretical support for its application in the treatment of functional constipation secondary to disuse muscle atrophy and gastrointestinal motility disorders.The study employed dexamethasone-induced in vitro cell models and tail suspension-induced in vivo mouse models to deeply analyze the regulatory effect of ghrelin on the PI3K-Akt-mTORC1 signaling pathway. Additionally, a loperamide-induced constipation mouse model was used to evaluate the effects of ghrelin on fecal output, gastric motility, and smooth muscle activity. Experimental methods included Western blotting, enzyme-linked immunosorbent assay, histopathological staining, phenol red assay, and Ca²⁺/ATP quantitative analysis to comprehensively assess the impact of ghrelin on muscle atrophy and gastrointestinal function.The results showed that ghrelin significantly upregulated the expression of p-AKT and reduced the level of p-Foxo3a in vitro, effectively alleviating muscle atrophy. In vivo, the muscle condition of mice improved, with decreased expression of atrophy-related proteins (MAFbx and MuRF1), promoting the functional recovery of hindlimb muscles. For constipated mice, ghrelin increased fecal water content and defecation frequency, and accelerated gastric emptying, which were consistent with the elevated levels of ghrelin in serum and tissues. Moreover, ghrelin promoted calcium ion influx and ATP production in gastric smooth muscle cells, thereby enhancing gastrointestinal motility.In conclusion, ghrelin effectively alleviates muscle atrophy by activating the PI3K-Akt-mTORC1 signaling pathway and improves gastrointestinal motility by enhancing smooth muscle activity. These findings highlight the potential of ghrelin as an effective therapy for functional constipation.