矢车菊素-3-葡萄糖苷改善胰岛功能及PVP-SPIO对胰岛示踪的应用

发布时间：2018-02-10 11:30

本文关键词： 胰岛移植糖尿病矢车菊素-3-葡萄糖苷氧化应激新生猪胰岛磁共振成像聚乙烯吡咯烷酮包裹的超顺磁氧化铁纳米颗粒　出处：《浙江大学》2015年博士论文　论文类型：学位论文

【摘要】：背景：胰岛移植是治疗胰岛素依赖糖尿病的有效方法,但仍然面临移植效率低、缺乏供体及有效的监测工具。胰岛由于本身缺乏抗氧化能力,难以耐受氧化应激的刺激。因此,本研究旨在探讨抗氧化剂矢车菊素-3-葡萄糖苷(C3G)能否改善移植入肾包膜下或门静脉的胰岛的功能。同时探究本课题组自主合成的聚乙烯吡咯烷酮包裹的超顺磁氧化铁纳米颗粒(PVP-SPIO)能否安全有效的监测移植的新生猪胰岛。方法： B6小鼠胰岛经不同浓度的C3G处理后,检测其存活率、抗氧化相关基因(HO-1)以及抗凋亡基因(β-catenin、Bcl-2和Survivn)的表达。监测经C3G(1.0μM)处理或未处理的B6小鼠胰岛(100，，200和400IEQ)移植入糖尿病B6小鼠的肾包膜下或门静脉内,监测其移植100天的血糖变化。PVP-SPIO标记的新生猪胰岛移植入免疫缺陷的糖尿病小鼠肾包膜下。小鼠在血糖正常后进行免疫重建。磁共振检测新生猪胰岛琼脂糖凝胶及接受移植及免疫重建的小鼠。结果：经C3G处理的胰岛较未处理的胰岛存活率明显提高,其HO-1、β-catenin、Bcl-2和Survivin的表达呈浓度依赖性升高。所有移植C3G处理胰岛的小鼠较移植未处理胰岛的小鼠更快的达到了正常血糖水平。肾包膜下移植400、200或100IEQ的C3G处理后胰岛的小鼠血糖均恢复正常,而在未处理组中,仅移植400和200IEQ的小鼠达到了正常血糖水平。门静脉内移植400和200IEQ经C3G处理胰岛的小鼠与400IEQ未处理胰岛的小鼠恢复了正常血糖。新生猪胰岛能够为MRI清楚地检测到。所有移植PVP-SPIO标记胰岛的小鼠均逆转了糖尿病。移植后第2天直至100天后,移植物能够被MRI检测到。免疫排斥后,移植物区域明显增大,并可见混合强度信号。结论：本研究的结果提示C3G能提高小鼠胰岛的存活率,改善其移植后的功能。PVP-SPIO标记不影响新生猪胰岛的功能,且可帮助检测移植的新生猪胰岛排斥发生前后的形态学变化。
[Abstract]:Background:. Islet transplantation is an effective method for the treatment of insulin-dependent diabetes mellitus, but it is still faced with low transplant efficiency, lack of donors and effective monitoring tools. Because of its lack of antioxidant capacity, islet transplantation is difficult to withstand the stimulation of oxidative stress. The purpose of this study was to investigate whether the antioxidant cornulin C 3G could improve the function of islets transplanted into the renal capsule or portal vein. At the same time, we investigated the superparamagnetic oxygen coated with polyvinylpyrrolidone. Iron nanoparticles PVP-SPIO) can safely and effectively monitor transplanted porcine islets. Methods:. The survival rate of B6 mouse islets treated with different concentrations of C3G was determined. The expression of anti-oxidation-related genes (HO-1) and anti-apoptotic genes (尾 -catenin Bcl 2 and survivvn) were monitored. B6 mice treated or untreated with C3GN 1.0 渭 M were transplanted into the renal capsule or portal vein of diabetic B6 mice. Monitoring the changes of blood glucose on 100 days after transplantation. PVP-SPIO-labeled neonatal porcine islets were transplanted under the renal capsule of immunodeficient diabetic mice. Immune reconstitution was performed in mice after normal blood glucose. Agarose gel of neonatal porcine islets was detected by magnetic resonance imaging (MRI). Mice receiving transplantation and immune reconstruction. Results:. The survival rate of islets treated with C3G was significantly higher than that of untreated islets. The expression of HO-1, 尾 -cateninine Bcl-2 and Survivin increased in a concentration-dependent manner. All C3G treated mice reached normal blood glucose levels faster than those of untreated islets. Small islets were treated with 400,200 or 100IEQ under renal capsule. The blood glucose of rats returned to normal. In the unprocessed group, Normal blood glucose levels were achieved in mice transplanted only to 400 and 200IEQ. Normal blood glucose was recovered in C3G treated mice and untreated islets of 400 and 200IEQ in portal vein. Neonatal porcine islets could be clearly detected for MRI. All mice transplanted with PVP-SPIO reversed diabetes. The grafts could be detected by MRI. After immune rejection, the graft region was obviously enlarged and mixed intensity signals could be seen. Conclusion:. The results of this study suggest that C3G can improve the survival rate of islets in mice and improve the function of transplanted islets. PVP-SPIO labeling does not affect the function of neonatal porcine islets, and can help to detect the morphologic changes before and after rejection of transplanted neonatal porcine islets.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R587.1

【共引文献】