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

中文关键词:  PI3K/Akt通路 脐带间充质干细胞 移植 缺氧缺血性脑损伤 机制

英文关键词:PI3K/Akt signaling pathway Umbilical cord-derived mesenchymal stem cells Transplantation

中文摘要:

      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。

英文摘要:

      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．