發(fā)布時(shí)間：2018-03-10 17:49

  本文選題：骨髓　切入點(diǎn)：間質(zhì)干細(xì)胞　出處：《中國組織工程研究》2016年14期 　論文類型：期刊論文

【摘要】：背景:骨髓間充質(zhì)干細(xì)胞移植入缺血心肌后存活率低,而低氧有可能增強(qiáng)骨髓間充質(zhì)干細(xì)胞的增殖,促進(jìn)其存活。目的:探討Pim-1激酶是否介導(dǎo)缺氧預(yù)處理對(duì)骨髓間充質(zhì)干細(xì)胞的保護(hù)作用及其機(jī)制。方法:設(shè)置不同低氧處理時(shí)間(0,6,12,24 h)處理骨髓間充質(zhì)干細(xì)胞,RT-qP CR及Western blot檢測(cè)Pim-1及凋亡相關(guān)基因的表達(dá),確定最佳低氧處理時(shí)間為12 h。將骨髓間充質(zhì)干細(xì)胞分為3組:正常對(duì)照組、低氧組、低氧+Pim-1抑制劑組,分別進(jìn)行Transwell遷移實(shí)驗(yàn)、細(xì)胞凋亡流式檢測(cè)、線粒體膜電位檢測(cè)評(píng)估各組骨髓間充質(zhì)干細(xì)胞的遷移能力及抗凋亡能力;建立心肌梗死模型,1周后按分組在大鼠梗死心肌周圍多點(diǎn)注射骨髓間充質(zhì)干細(xì)胞,2周后制備心肌冰凍切片行DiI染色統(tǒng)計(jì)骨髓間充質(zhì)干細(xì)胞存活數(shù)量;心肌梗死模型建立前后、細(xì)胞移植4周行超聲心動(dòng)圖檢查評(píng)估大鼠心臟功能。結(jié)果與結(jié)論:(1)低氧處理12 h時(shí),骨髓間充質(zhì)干細(xì)胞的Pim-1、p-Akt及Bcl-2表達(dá)量明顯升高,Bax、Caspase-3表達(dá)量明顯降低。(2)低氧組骨髓間充質(zhì)干細(xì)胞抗凋亡能力明顯增強(qiáng),與正常對(duì)照組之間差異有顯著性意義(P0.01)。(3)低氧組骨髓間充質(zhì)干細(xì)胞移植1周后存活率明顯提高(P0.001);移植4周后,大鼠心功能明顯改善(P0.05)。上述獲益可被Pim-1抑制劑抑制。(4)結(jié)果證實(shí),低氧預(yù)處理骨髓間充質(zhì)干細(xì)胞通過激活A(yù)kt及上調(diào)Pim-1表達(dá)抑制細(xì)胞凋亡,改善骨髓間充質(zhì)干細(xì)胞對(duì)缺血性心臟病的治療效果。
[Abstract]:Background: the survival rate of bone marrow mesenchymal stem cells after transplantation into ischemic myocardium is low, but hypoxia may enhance the proliferation of bone marrow mesenchymal stem cells. Objective: to investigate the protective effect of Pim-1 kinase mediated hypoxia preconditioning on bone marrow mesenchymal stem cells (BMSCs) and its mechanism. Methods: bone marrow mesenchymal stem cells were treated with RT-qP CR and RT QP CR for 24 h. Western blot was used to detect the expression of Pim-1 and apoptosis-related genes. The optimal hypoxia treatment time was 12 h. Bone marrow mesenchymal stem cells were divided into three groups: normal control group, hypoxic group and hypoxic Pim-1 inhibitor group. Transwell migration assay and apoptosis were detected by flow cytometry. The migration and anti-apoptosis ability of bone marrow mesenchymal stem cells were evaluated by mitochondrial membrane potential assay. One week after myocardial infarction model was established, myocardial frozen sections were prepared after multiple injection of bone marrow mesenchymal stem cells into the infarcted myocardium of rats for 2 weeks. DiI staining was used to calculate the number of bone marrow mesenchymal stem cells survival. Before and after the establishment of myocardial infarction model, the survival rate of bone marrow mesenchymal stem cells was calculated. After 4 weeks of transplantation, echocardiography was performed to evaluate cardiac function in rats. The expression of Pim-1p-Akt and Bcl-2 in bone marrow mesenchymal stem cells (BMSCs) increased significantly. The expression of Caspase-3 in Bax-Caspase-3 decreased significantly. The survival rate of bone marrow mesenchymal stem cells in hypoxic group increased significantly after 1 week of transplantation, and the cardiac function of rats improved significantly after 4 weeks of transplantation. The above benefits could be confirmed by the inhibition of Pim-1 inhibitor (P0. 05), and the difference between the two groups was significant (P 0. 01, P 0. 01, P 0. 01, P 0. 01, P 0. 01, P 0. 01, P 0. 01, P 0. 01, P 0. 01). Hypoxic preconditioning of bone marrow mesenchymal stem cells inhibited apoptosis by activating Akt and up-regulating the expression of Pim-1, thus improving the therapeutic effect of bone marrow mesenchymal stem cells on ischemic heart disease.
【作者單位】： 蘇州大學(xué)附屬第一醫(yī)院心內(nèi)科;蘇州大學(xué)附屬第一醫(yī)院心外科;蘇州大學(xué)心血管病研究所;
【分類號(hào)】：R457.7

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