关键词: 丙泊酚, 骨质疏松症, 骨代谢, PI3K/AKT/mTOR信号通路, 自噬

Abstract: Objective To investigate the effect of propofol on bone metabolism in glucocorticoid induced osteoporo-sis (GIOP) in rat models by regulating the PI3K/AKT/mTOR signaling pathway. Methods Rats were grouped into a blank group, model (GIOP) group, 2.5 mg/kg and 5 mg/kg propofol groups and a propofol+LY294002 (5 mg/kg propofol+5 mg/kg LY294002) group, with 12 rats in each group. A small animal bone densitometer was used to measure the tibial bone density (BMD) of rats. ELISA was applied to detect the level of bone gla-protein (BGP), procollagen Ⅰ N-terminal propeptide (PINP) and type Ⅰ collagen cross-linked C-terminal peptide (CTX-Ⅰ) in rat serum. HE staining microscopy was applied to observe the pathological morphology of rat bone tissue. RT-qPCR was used to detect the mRNA expression of Pi3k, Akt, mTor, Beclin-1, and p62 in bone tissue. Western blot was used to detect the expression level of PI3K/AKT/mTOR signaling pathway related proteins and autophagy related proteins in rat bone tissue. Results Compared with the blank group, the tibial BMD, serum BGP, and CTX-Ⅰ levels of GIOP group decreased (P＜0.05). mRNA expression of Pi3k, Akt, mTor and Beclin-1 in bone tissue decreased (P＜0.05). mRNA and protein expression of p62 increased (P＜0.05). The expression of PI3K/AKT/mTOR signaling pathway related proteins and Beclin-1 protein in bone tissue decreased(P＜0.05). Compared to GIOP group, the changes of above indicators were obviously alleviated in the 2.5 mg/kg and 5 mg/kg propofol groups (P＜0.05). On the basis of treatment with 5 mg/kg propofol, the use of LY294002 inhibited activation of the PI3K/AKT/mTOR signaling pathway and autophagy and interfered with the positive regulatory effects of propofol on bone metabolism and bone tissue morphology improvement in GIOP rats (P＜0.05). Conclusions Propofol may improve bone metabolism in rat models of GIOP through potential mechanism of activating PI3K/AKT/mTOR signaling pathway.

Key words: propofol, osteoporosis, bone metabolism, PI3K/AKT/mTOR signaling pathway, autophagy