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.%背景:研究已证实,丙泊酚可减少成年大鼠间充质干细胞的数量,同时与间充质干细胞相关的分化也显著受到抑制.目的:探究肝X受体是否可激活修复丙泊酚对骨髓间充质干细胞的抑制作用.方法:将15只新生C57/BL6小鼠随机分为3组,空白对照组腹腔注射生理盐水;对照组腹腔注射丙泊酚60 mg/kg;实验组首先腹腔注射肝X受体激动剂10μL/g,隔天注射丙泊酚60 mg/kg.注射1-3 h后处死3组小鼠,分离培养骨髓间充质干细胞,CCK-8及克隆形成实验检测细胞增殖及自我更新情况;检测3组细胞的成脂、成骨及成软骨能力;实时定量PCR检测3组细胞诱导分化前、诱导分化后的Notch信号表达,以及加入Notch通路抑制剂后,成脂、成骨及成软骨诱导分化后的相关基因表达.结果与结论:①与空白对照组比较,对照组骨髓间充质干细胞增殖与克隆形成能力显著降低(P<0.05);与对照组比较,实验组骨髓间充质干细胞增殖与克隆形成能力显著升高(P<0.05);②与空白对照组比较,对照组骨髓间充质干细胞成脂、成骨及成软骨能力显著降低(P<0.05);与对照组比较,实验组骨髓间充质干细胞成脂、成骨及成软骨能力显著升高(P<0.05);③诱导分化前,3组间Notch信号表达无差异.诱导分化后,与空白对照组比较,对照组骨髓间充质干细胞成脂、成骨及成软骨分化相关基因表达显著下调(P<0.05);与对照组比较,实验组骨髓间充质干细胞成脂、成骨及成软骨分化相关基因表达显著上调(P<0.05).加入Notch通路抑制剂后,3组细胞成脂、成骨及成软骨诱导分化均受抑制;④结果表明,肝X受体激活可修复丙泊酚对骨髓间充质干细胞的抑制作用.
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