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PI3K/Akt通路在UC-MSCs移植治疗新生大鼠HIBD中的作用机制

Umbilical Cord-derived Mesenchymal Stem Cells Grafts for Neonatal Rats Model of HIBD: the Mechanism of PI3K/Akt Signaling Pathway

  • 摘要: 目的 探讨磷脂酰肌醇3激酶/蛋白激酶B (PI3K/Akt)通路在脐带间充质干细胞(UC-MSCs)移植治疗新生大鼠缺氧缺血性脑损伤(HIBD)中的机制。方法 10日龄SD大鼠分为假手术组、移植组(MSCs组)、抑制剂组(LY组)及HIBD组,制作HIBD动物模型,5-溴脱氧嘧啶尿苷标记UC-MSCs后侧脑室移植,移植后24 h、48 h, TUNEL、Western blot分别检测细胞凋亡及caspase3、磷酸化Akt(P-Akt)蛋白表达。结果 移植后24 h、48 h, MSCs组细胞凋亡数及caspase3蛋白表达量较LY组及HIBD组减少( P<0.05),而P-Akt表达较LY组及HIBD组增加( P<0.05),且随移植后时间的延长,各指标的表达均呈下降趋势( P<0.05)。结论 UC-MSCs移植治疗HIBD新生大鼠时,脑组织细胞凋亡减少,caspase3表达下调,P-Akt表达上调,PI3K/Akt信号通路可能为其重要机制。

     

    Abstract: Objective To determine the physicochemical properties of iRGD conjugated doxorubicin loaded liposome (iRGD-LP-DOX), and its effect on targeting and inhibiting growth of A549 cells. Methods Liposomes were observed under a transmission electron microscope. Release of doxorubicin from iRGD-LP-DOX was detected by the dialysis bag method. The efficiency of cellular uptake and tumor spheroids penetration on A549 cells in vitro was determined. The anti-proliferation efficiency of iRGD-LP-DOX was evaluated by MTT assay using IC 50 (50% inhibition concentration). Results iRGD-LP-DOX was spherical in a uniform size. Free DOX was released by 100% in 5 h, while LP-DOX and iRGD-LP-DOX were released by about 40% in 48 h. A higher level of iRGD-LP-DOX uptaken by A549 was found compared with that of LP-DOX ( P<0.01). Higher fluorescence intensity was detected with iRGD-LP-DOX than with LP-DOX in tumor spheroid. The MTT assay confirmed strong inhibitory effect of iRGD-LP-DOX ( P<0.01). Conclusion iRGD can enhance uptake of liposomes by A549 cells and inhibit the proliferation of tumor cells.

     

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