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    不同药物-靶点停留时间的腺苷A1受体激动剂对肠细胞缺血再灌注的影响

    Effects of adenosine A1 receptor agonists with different residence times on intestinal ischemia reperfusion

      摘要
    • 摘要:
      目的： 探讨腺苷A1受体激动剂的药物-靶点停留时间（RT）对肠细胞缺血再灌注的影响。
      方法： 体外培养人结肠癌细胞系Caco-2，构建氧-葡萄糖剥夺/复氧（OGD/R）模型，在细胞进行OGD/R之前，加入不同RT的腺苷A1受体激动剂（CPA和LUF6941），通过使用PI染色、CCK-8实验检测细胞存活率以及细胞活力，并采用Western boltting实验检测细胞中PI3K的表达和Akt的磷酸水平。
      结果： 在肠细胞进行OGD/R期间，CPA和LUF6941能够降低细胞凋亡率和增强细胞活力（P ＜ 0.05和P ＜ 0.001），CPA和LUF6941能够增加PI3K的表达（P ＜ 0.01），促进Akt的磷酸化（P ＜ 0.01）；同时，具有长RT的LUF6941的药理作用比具有短RT的CPA强（P ＜ 0.05）。
      结论： 在肠细胞进行OGD/R期间，不同RT的腺苷A1受体激动剂能够通过激活PI3K/Akt信号通路，降低细胞凋亡，增强细胞活力且具有较长RT的激动剂具有较强的药理作用。

       

      Abstract:
      Objective To investigate the effect of drug target residence time (RT) of adenosine A1 receptor agonists on intestinal ischemia reperfusion.
      Methods Human colon cancer cell line Caco-2 was cultured in vitro to establish an oxygen glucose deprivation/reoxygenation (OGD/R) model. Before OGD/R, adenosine A1 receptor agonists (CPA and LUF6941) with different RTs were added to the cells. Cell survival and viability were measured using PI reagents and CCK-8. Western blot assay was used to detect the expression of PI3K and the level of Akt phosphate in the cells.
      Results During OGD/R of intestinal cells, CPA and LUF6941 could reduce the rate of apoptosis (P ＜ 0.05 and P ＜ 0.01) and enhance cell viability (P ＜ 0.05 and P ＜ 0.001), while CPA and LUF6941 could increase the expression of PI3K (P ＜ 0.01) and promote the phosphorylation of Akt (P ＜ 0.01); At the same time, the pharmacological effect of LUF6941 with long RT was stronger than that of CPA with short RT (P ＜ 0.05).
      Conclusion During OGD/R in intestinal cells, adenosine A1 receptor agonists with different RTs can reduce apoptosis and enhance cell viability by activating the PI3K/Akt signaling pathway. Agonists with longer RT have stronger pharmacological effects.

       

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