糖尿病相关细胞模型的建立及天然组分作用研究
文献类型：学位论文
| 作者 | 张明旭 |
| 学位类别 | 硕士 |
| 答辩日期 | 2000-06 |
| 授予单位 | 中国科学院研究生院 |
| 导师 | 傅德贤 |
| 关键词 | 糖尿病 模型 天然组分 筛选 |
| 其他题名 | Research on the Cell Model Associated with Diabetes Mellitus and the Effect of Natural Products |
| 学位专业 | 生物化工 |
| 中文摘要 | 糖尿病是一类严重危害人类健康的疾病。据估计，全世界约有1.25亿患者，其中许多病人合并心、肾、眼等慢性病变。世界各国每年耗费世资对该病进行防治研究，但尚缺乏有效的措施。我国传统医学早在数千年前就有糖尿病（消渴病）及其并发症的记载。近年来，中国中医药、中西医结合学界在糖尿病尤其是并发症防治研究方面取得了不少成就。在我国的天然产物中，特别是传统药、民间药和海洋生物中寻找和筛选活性成份，寻找有治疗糖尿病潜力的新药，有可能是一种有效的途径。胰岛素依赖型糖尿病是糖尿病的一类，它是由于胰岛中分泌胰岛素的β细胞被免疫性破坏而导致的慢性疾病。研究发现细胞因子IL-1β对分离培养的胰岛β细胞有特异地细胞毒性。我们观察了不同浓度IL-1β（1U/ml、5U/ml、10U/ml）对β细胞分泌胰岛素和葡萄糖刺激下分泌胰岛素的影响。发现1U/ml IL-1β能够使胰岛素的分泌量减少的同时有一氧化氮（NO）自由基产生增多，而基础胰岛分泌减少未见到NO变化。这可能说明NO是细胞因子破坏胰岛细胞分泌功能中重要的但不是唯一的因素。同时我们发现IL-1β对β细胞的毒性作用能被TNFα强化。因而我们用IL-β与胰岛细胞共同培养建立了胰岛细胞损伤模型。高血糖是发生糖尿病血管并发症的主要原因。本文研究观察了不同浓度葡萄糖环境下内皮细胞的生长情况。结果证实，培养环境中较高浓度的葡萄糖将导致短期培养的内皮细胞（48h、72h）增殖缓慢、死亡细胞数增多。含30mM葡萄糖的培养液作用于内皮细胞造成的损伤可以作为糖尿病并发症的一种实验模型。对5种中草药和海洋低等生物中提取的47个天然组分分别应用胰岛细胞损伤模型、内皮细胞损伤模型以及T淋巴细胞增殖抑制模型进行了活性研究。结合3种细胞模型的实验结果，发现一组分具有保护胰岛细胞，防止高糖对内皮细胞的损伤或抑制T淋巴细胞的活性成分。 |
| 英文摘要 | Diabetes Mellitus is now becoming a serious problem threatening the people's health. It is predicted that there are 120 million of diabetics all over the world now, and a large number of them are suffering from its chronic complications of heart, kidney, eye, etc. Lots of efforts have been paid on the prevention, treatment and research of the disease, but there is still lack of satisfactory result. Traditional Chinese Medicine recorded Diabetes (Xiao Ke Disease) and its complications as early as several thousand years ago. In recent years, Traditional Chinese Medicine and Pharmacy, combination of Chinese and Western Medicine have acquired lots of achievement in the research of preventing and treating Diabetes especially it's complications. Screening the potential drugs from the natural products, including the traditional herbal medicine, marine creatures, can be an effective method. As one type of diabetes mellitus, insulin-dependent diabetes mellitus (IDDM) is a serious chronic disease caused by immune-mediated destruction of the insulin-secreting β cells in the islets of Langerhans. The basis of the present studies was the initial finding that the cytokine interleukin-1β (IL-1β) was selectively cytotoxic to β-cells in isolated islets of Langerhans. We investigated the effect of different concentration of IL-1β (1-U/ml, 5U/ml, 10U/ml) on the insulin secretion and glucose-stimulated secretion of β cells and found that 1U/ml IL-1β could reduce the islet insulin release. With the decrease of glucose-stimulated insulin secretion, the production of the free radical oxide (NO) increased, but there was no NO change when the basic insulin secretion reduced. This may be lead to the conclusion that NO is an important, but not the unique, mediator of the deleterious effects of cytokines on islet function. Moreover, we found that IL-1β is cytotoxic to β cells through the induction of free radicals in the islets and can be potentiated by TNFα. Thus we established the β cell destruction model through incubating the islets with 1 U/ml IL-1β. Hyperglycemia is a major cause of vascular complications in diabetes in vivo. We examined the proliferation of vascular endothelial cells cultured in the medium with different glucose concentration (5mM, 20mM, 30mM, 50mM). The results convinced that high ambient glucose could delay the replication and induce excess cell death in cultured endothelial cells for short-term (48, 72h) experiments. We could regard the endothelial cell destruction after short-term incubation in 30 mM glucose as the model of diabetes vascular complications. The effects of 47 natural extracts from marine creatures and traditional medicine have been investigated by the methods discussed above, e.g., the model of islets destruction, the model of endothelial destruction and experiment of T lymphocytes proliferation. Some active components among the natural products have been found having the effect of protecting islets cells, preventing endothelial cells from destruction in high ambient glucose or inhibiting the T lymphocytes functions. |
| 语种 | 中文 |
| 公开日期 | 2013-09-26 |
| 页码 | 72 |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/1944]  |
| 专题 | 过程工程研究所_研究所（批量导入） |
| 推荐引用方式 GB/T 7714 | 张明旭. 糖尿病相关细胞模型的建立及天然组分作用研究[D]. 中国科学院研究生院. 2000. |
入库方式： OAI收割
来源：过程工程研究所
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