發(fā)布時(shí)間：2018-01-08 09:08

  本文關(guān)鍵詞：多模態(tài)成像檢測(cè)干細(xì)胞聯(lián)合功能化自組裝多肽治療急性心肌梗死　出處：《北京協(xié)和醫(yī)學(xué)院》2017年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 骨髓間充質(zhì)干細(xì)胞 功能化自組裝多肽納米支架 急性心肌梗死 心功能 SPECT/CT PET/CT

【摘要】：目的:利用攝取碘-131標(biāo)記的ZGO的SD大鼠骨髓間充質(zhì)干細(xì)胞(BMSCs),聯(lián)合功能化自組裝納米多肽支架RADA-SKP注射至Balb/c小鼠急性梗死的心肌周圍,利用超聲心動(dòng)、SPECT/CT、PET/CT多模態(tài)的影像手段,評(píng)估心功能變化,示蹤BMSCs的定位、存活和遷移,評(píng)估心肌活性變化,同時(shí)結(jié)合病理結(jié)果,探討功能化自組裝多肽納米支架材料提高干細(xì)胞在急性心肌梗死治療中,提高治療效果的可能性及其機(jī)制。方法:構(gòu)建Balb/c小鼠的急性心肌梗死模型,分別在梗死心肌周圍注射:A組(空白對(duì)照組):10%蔗糖溶液;B組(多肽對(duì)照組):功能化自組裝納米多肽支架RADA-SKP的蔗糖溶液;C組(細(xì)胞對(duì)照組):吞噬碘-131標(biāo)記的ZGO的BMSCs;D組(多肽+細(xì)胞實(shí)驗(yàn)組):吞噬碘-131標(biāo)記的ZGO的BMSCs聯(lián)合功能化自組裝納米多肽支架RADA-SKP的蔗糖溶液。在術(shù)前1天和術(shù)后第1、7、14天行超聲心動(dòng)評(píng)估心功能;在術(shù)后第1、6、13天行SPECT/CT定位移植細(xì)胞;術(shù)后第2、14天行PET/CT評(píng)估梗死區(qū)域心肌活性。術(shù)后第14天取出心臟組織病理,行HE染色及CD34免疫組化。結(jié)果:心功能方面:利用功能化自組裝多肽納米支架RADA-SKP能夠顯著提高BMSCs對(duì)于小鼠心肌梗死模型的治療效果。而單純利用BMSCs治療小鼠心肌梗死模型對(duì)于心功能的改善并無顯著效果。干細(xì)胞定位方面:提示利用BMSCs聯(lián)合功能化自組裝納米多肽支架進(jìn)行治療相較于單用BMSCs,能夠使細(xì)胞更長(zhǎng)時(shí)間的保持細(xì)胞的活性。梗死區(qū)域心肌活性方面:利用功能化自組裝多肽RADA-SKP聯(lián)合BMSCs對(duì)于小鼠心梗模型治療相較于空白對(duì)照組和只移植功能化自組裝多肽RADA-SKP組,能夠顯著改善心肌的活性。同時(shí),在不聯(lián)用功能化自組裝多肽SKP的情況下,對(duì)于BMSCs修復(fù)梗死區(qū)域心肌的活性的修復(fù),與聯(lián)用功能化自組裝多肽RADA-SKP的情況下,無顯著性差異。結(jié)論:利用攝取碘-131標(biāo)記的ZGO的大鼠BMSCs注射至Balb/c小鼠急性心肌梗死的心肌周圍,利用超聲心動(dòng)、SPECT/CT、PET/CT多模態(tài)檢測(cè),可以有效的評(píng)估心功能變化,示蹤BMSCs的定位、存活和遷移,評(píng)估心肌活性變化。單純將SD大鼠BMSCs注射至Balb/c小鼠急性心肌梗死的心肌周圍,可以改善心肌活性,但細(xì)胞存活時(shí)間較短,對(duì)于心功能的改善不明顯;而聯(lián)合功能化自組裝納米多肽支架RADA-SKP時(shí),可以延長(zhǎng)BMSCs在心肌中存活的時(shí)間,加強(qiáng)其誘導(dǎo)血管分化的作用,強(qiáng)化治療效果。
[Abstract]:Objective: to investigate the effects of iodine 131 labeled ZGO on bone marrow mesenchymal stem cells (BMSCs) in SD rats. RADA-SKP was injected into the myocardium around acute infarction of Balb/c mice and SPECT / CT was used. PET/CT multimodal imaging method to assess cardiac function changes, trace the location, survival and migration of BMSCs, and evaluate myocardial activity changes, combined with pathological results. Objective: to explore the possibility and mechanism of functional self-assembled polypeptide nano-scaffold to improve the therapeutic effect of stem cells in acute myocardial infarction (AMI). Methods: the acute myocardial infarction model of Balb/c mice was established. Group A was injected with 10% sucrose solution around the infarct myocardium. Group B (polypeptide control group): sucrose solution of functionalized self-assembled nano-polypeptide scaffold RADA-SKP; Group C (cell control group): BMSCsphagocytosis of iodine-131 labeled ZGO; Group D (polypeptide cell test group). Phagocytosis of sucrose solution of iodo-131 labeled ZGO BMSCs combined with functionalized RADA-SKP nano-polypeptide scaffold. 1 day before and 1 day after operation. Cardiac function was evaluated by echocardiography on day 7 and 14; The transplanted cells were treated with SPECT/CT on the 1st day and 13th day after operation. Myocardial activity in the infarcted area was evaluated by PET/CT on the 2nd and 14th day after operation, and cardiac histopathology was taken out on the 14th day after operation. He staining and CD34 immunohistochemistry. Results: heart function:. The use of functionalized self-assembled polypeptide nano-scaffold RADA-SKP can significantly improve the therapeutic effect of BMSCs on myocardial infarction model in mice, while BMSCs alone can be used to treat myocardial infarction model in mice. There was no significant improvement in cardiac function. Stem cell localization:. It is suggested that BMSCs combined with functionalized self-assembled nano-polypeptide scaffold is more effective than BMSCs alone. The ability to keep cells alive for a longer period of time. Myocardial activity in infarcted areas:. Compared with control group and RADA-SKP group, functional self-assembled polypeptide (RADA-SKP) combined with BMSCs was used to treat myocardial infarction model in mice. At the same time, without the use of functional self-assembled polypeptide SKP, the repair of myocardial activity in infarcted area by BMSCs can be significantly improved. In conjunction with functionalized self-assembled polypeptide RADA-SKP. No significant difference was found. Conclusion: rat BMSCs with iodine-131-labeled ZGO was injected into the myocardium around the acute myocardial infarction of Balb/c mice and echocardiography was used. SPECT / CT / PET / CT multimodal detection can effectively evaluate cardiac function changes, trace the location, survival and migration of BMSCs. To evaluate the changes of myocardial activity. Injection of SD rat BMSCs into myocardium around acute myocardial infarction in Balb/c mice could improve myocardial activity, but the cell survival time was shorter. The improvement of cardiac function was not obvious. When RADA-SKP was combined with functionalized self-assembled nano-polypeptide scaffold, the survival time of BMSCs in myocardium was prolonged, the effect of inducing vascular differentiation was enhanced, and the therapeutic effect was enhanced.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R542.22

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