Liver X receptor reverses the inhibitory effects of propofol on bone marrow mesenchymal stem cells / 中国组织工程研究

ABSTRACT

BACKGROUND: Studies have shown that propofol enables a reduction in the number of adult rat mesenchymal stem cells, while the cell differentiation is also significantly inhibited. OBJECTIVE: To explore whether liver X receptors (LXRs) can reverse the inhibitory effects of propofol on bone marrow mesenchymal stem cells. METHODS: Fifteen healthy C57/BL6 mice were randomized into three groups, 5 of which served as blank control group (intraperitoneally treated with normal saline), 5 as propofol treatment group (intraperitoneally treated with 60 mg/kg propofol), and 5 as propofol + LXRs agonist treatment group (intraperitoneally injected with 10 μL/g LXRs at the 1st day, and then injected with 60 mg/kg propofol at the 2nd day). The mice in the three groups were killed at 1-3 hours after treatment to isolate and culture bone marrow mesenchymal stem cells. Cell counting kit-8 and cloneformation assay were used to evaluate the abilities of cell proliferation and self-renewal; induced differentiation experiments in vitro were used to evaluate the differentiation ability of cells into adipocytes, osteoblasts and chondrocytes; real-time quantitative PCR was used to detect the expression of differentiation related molecules andNotch signal. RESULTS AND CONCLUSION: In the propofol-treated mice, cell viability and clone forming ability as well as adipogenic, osteogenic and chondrogenic differentiation of cells decreased significantly compared with the blank control group (P <0.05), while LXR agonists could reverse these effects significantly (P < 0.05). Notch signal expressions showed no difference among three groups prior to induced differentiation. The expression levels differentiation related molecules downregulated significantly after propofol treatment (P < 0.05), but upregulated significantly after treatment with LXR agonists (P < 0.05). Notch signaling inhibitor treatment could significantly inhibit the multi-directional differentiation of bone marrow mesenchymal stem cells in the three groups. All these findings indicate that activated LXRs can reverse the inhibitory effects of propofol on bone marrow mesenchymal stem cells.