本文選題：納米粒子　切入點：藥物載體　出處：《安徽醫(yī)科大學》2014年碩士論文

【摘要】：研究背景及目的 近年來隨著抗腫瘤藥物的迅速發(fā)展，化療在膠質(zhì)瘤治療中的地位越來越重要。阿霉素（doxorubicin，DOX）是臨床上最常用的抗腫瘤藥物之一，它抗腫瘤活性強，但其對正常組織和器官的毒副作用大，這嚴重限制了其在腫瘤治療中的應用。因此構(gòu)建一種可以攜帶DOX導向性藥物輸送載體對腫瘤治療的研究具有非常重要的意義。本論文選用葉酸（folic acid，F(xiàn)A）修飾的載DOX Mn納米粒子體系，不僅能使DOX在膠質(zhì)瘤病灶部位富集，還可以通過MRI監(jiān)測藥物在體內(nèi)的分布。 本實驗利用Mn納米粒子對大鼠C6膠質(zhì)瘤腦內(nèi)及皮下腫瘤模型進行3T磁共振成像，并對它們的成像特征進行研究，可以更真實的觀測腫瘤的生長規(guī)律；利用磁共振活體示蹤法并且結(jié)合HE染色證實FA修飾的載DOX Mn納米粒子體系對大鼠C6膠質(zhì)瘤的治療效果。 材料和方法 10只，SD大鼠，清潔級，，雄性，250-280g；收集對數(shù)生長期的鼠C6膠質(zhì)瘤細胞，建立大鼠C6腦膠質(zhì)瘤模型，接種7d后行MR掃描，然后通過鼠尾靜脈注射0.5ml Mn納米粒子，分別于注射后5min、24h再次行MR掃描，掃描結(jié)束后取出腦內(nèi)腫瘤組織行HE染色。10只，SD大鼠，清潔級，雄性，150-180g，收集對數(shù)生長期大鼠C6膠質(zhì)瘤細胞，建立大鼠C6皮下膠質(zhì)瘤模型，接種第7d先行MR平掃，再通過鼠尾靜脈注射0.5ml Mn納米粒子，分別于注射后5min、1h再次行MR掃描，掃描結(jié)束后剝離皮下腫瘤，行HE染色。建立大鼠C6皮下膠質(zhì)瘤模型20只，隨機分為四組，于接種后第10、11、12、14d分別經(jīng)鼠尾靜脈注射0.5ml FA修飾的載DOX Mn納米粒子(FA-Mn-DOX)、生理鹽水、DOX、載DOX Mn納米粒子（Mn-DOX），接種后的10-18d荷瘤鼠每天行MR掃描，MR掃描采集的圖像傳至ADW4.4工作站，在腫瘤最大層面測量腫瘤的最長徑（L）、最寬徑（W），計算腫瘤的體積；隨后將腫瘤完整剝離下來，石蠟包埋后行HE染色。 結(jié)果 成功建立了大鼠C6腦膠質(zhì)瘤模型、大鼠C6皮下膠質(zhì)瘤模型，并用Mn納米粒子對腫瘤實現(xiàn)MR成像， MRI檢測更準確反映腦內(nèi)、皮下C6膠質(zhì)瘤呈指數(shù)的生長規(guī)律。自第1次給藥后至第18d各時間段，與對照組相比，實驗各組腫瘤體積均有不同程度的下降，差異有統(tǒng)計學意義（P0.05）；HE染色見FA-Mn-DOX組、DOX組、Mn-DOX組腫瘤細胞發(fā)生了一系列不可逆損害變化，其中以FA-Mn-DOX組最為顯著。 結(jié)論 應用Mn納米粒子對大鼠C6膠質(zhì)瘤活體示蹤MR成像，可以反映腫瘤的生物學特性，適用于腫瘤生長規(guī)律的觀察和實驗性治療效果的評價；FA-Mn-DOX系一種多功能納米藥物載體，可作為磁共振靶向造影劑的同時，還具有雙靶向治療的作用，對大鼠C6皮下膠質(zhì)瘤具有診斷和治療的雙重作用。
[Abstract]:Research background and purpose. In recent years, with the rapid development of antitumor drugs, chemotherapy is becoming more and more important in the treatment of glioma. Doxorubicin doxorubicin doxorubin dox is one of the most commonly used antitumor drugs in clinic, and it has strong antitumor activity. But its toxic side effects on normal tissues and organs are great. Therefore, it is very important to construct a carrier carrying DOX oriented drug delivery vector for the study of tumor therapy. In this paper, folic acid folic acid FA-FA-modified DOX mn nanoparticles system was selected. It can not only enrich DOX in glioma foci, but also monitor the distribution of drugs in vivo by MRI. In this experiment, 3T magnetic resonance imaging was performed on C6 glioma brain and subcutaneous tumor models using mn nanoparticles, and their imaging characteristics were studied, so that the growth law of C6 glioma could be observed more truthfully. The effect of FA modified DOX mn nanoparticles system on C6 glioma in rats was confirmed by in vivo magnetic resonance tracer method and HE staining. Materials and methods. Ten SD rats, clean grade, male, 250-280 g.The C6 glioma cells in logarithmic growth phase were collected, and the rat C6 glioma model was established. After 7 days of inoculation, Mr scanning was performed, and then 0.5ml mn nanoparticles were injected into the tail vein of rats. Mr scanning was performed again at 5 min and 24 h after injection. After the scan, 10 SD rats were stained with HE. The C6 glioma model was established by collecting C6 glioma cells in logarithmic phase of C6 glioma rats. On the 7th day of inoculation, Mr plain scan was performed first, then 0.5ml mn nanoparticles were injected into the tail vein of mice. Mr scanning was performed again at 5 min and 1 hour after injection. The subcutaneous tumor was stripped off and stained with HE after the scanning. Twenty rat C6 subcutaneous glioma models were established. Four groups were randomly divided into four groups. On the 10th day after inoculation, the DOX mn nanoparticles modified by 0.5ml FA were injected into the tail vein of mice at 14 days after inoculation. The DOX mn nanoparticles (FA-Mn-DOXX), normal saline dox and DOX mn nano-particles were injected into the tail vein of mice respectively. The images collected by Mr scanning were transmitted to ADW4.4 workstation every day on 10-18 days after inoculation. The maximum diameter of the tumor was measured at the maximum level of the tumor, and the volume of the tumor was calculated. Then, the tumor was stripped off completely and stained with HE after paraffin embedded. Results. The rat C6 glioma model and rat C6 subcutaneous glioma model were successfully established. Mr imaging of the tumor was realized with mn nanoparticles, and the brain was more accurately reflected by MRI detection. The growth pattern of subcutaneous C6 glioma was exponential. From the first administration to the 18th day, compared with the control group, the tumor volume of each experimental group decreased in varying degrees. The difference was statistically significant (P 0.05) and HE staining showed that there were a series of irreversible changes in tumor cells in FA-Mn-DOX group, especially in FA-Mn-DOX group. Conclusion. The in vivo tracer Mr imaging of rat C6 glioma with mn nanoparticles can reflect the biological characteristics of the tumor. It is suitable for the observation of tumor growth and the evaluation of experimental therapeutic effect. FA-Mn-DOX is a multifunctional nano-drug carrier. It can be used as Mr target contrast agent and can also be used as a double target therapy for C6 subcutaneous glioma in rats, and it can be used in the diagnosis and treatment of C6 subcutaneous glioma.
【學位授予單位】：安徽醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R739.41;R445.2

【參考文獻】

相關期刊論文 前4條

1 陳駿,余永強,錢銀鋒,張誠,沈玉先,張玲玲;大鼠C6腦膠質(zhì)瘤生長的動態(tài)觀察和MR灌注成像可行性研究[J];中華神經(jīng)醫(yī)學雜志;2004年01期

2 王曉剛,魏學忠,周定標;Wistar大鼠C_6膠質(zhì)瘤動物模型的腫瘤生長特點[J];軍醫(yī)進修學院學報;2001年04期

3 李明,馮華,李飛,王憲榮,吳南,陳志,吳國材,盧佳友,林江凱;大鼠C6腦膠質(zhì)瘤模型的病理特征與MRI的觀察[J];中華神經(jīng)外科雜志;2005年05期

4 王中領;郭亮;李勇剛;陳銦銦;顧宏偉;魯英杰;;葉酸靶向超順磁性氧化鐵-多巴胺-葉酸納米復合物的制備及體外MR成像[J];中國醫(yī)學影像技術;2011年02期

本文編號：1679457