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高浓度葡萄糖对胰岛细胞凋亡及凋亡相关基因的影响 被引量:12

Study on the Effects of High Concentration Glucose on Islet Cell Apoptosis and Apoptosis Related Gene
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摘要 目的:观察高浓度葡萄糖体外对胰岛细胞凋亡及凋亡相关基因表达的影响,探讨葡萄糖毒性及其分子机制。方法:应用TUNEL法检测高浓度葡萄糖培养后大鼠胰岛细胞和小鼠βTc3细胞凋亡百分率;应用定量RT-PCR(QRT-PCR)检测培养后大鼠胰岛细胞和小鼠βTc3细胞bcl-2和baxmRNA的表达;应用定量RT-PCR检测低剂量链脲佐菌素糖尿病大鼠胰岛bcl-2和baxmRNA的表达。结果:高浓度葡萄糖使原代培养的大鼠胰岛细胞和βTc-3的凋亡细胞比例明显增加;胰岛细胞凋亡过程中,诱导凋亡基因bax的mRNA表达水平明显升高,抵抗凋亡基因bcl-2mRNA表达水平明显下降,致使bcl-2/bax比率明显降低;对低剂量链脲佐菌素糖尿病大鼠胰岛凋亡相关基因QRT-PCR检测也显示同样的结果。结论:高浓度葡萄糖可能通过诱导胰岛细胞凋亡增加而加重糖尿病,其中bcl-2/baxmRNA表达比率变化可能起重要作用。 Objective: To study the effects of high concentration glucose on islet cell apoptosis and apoptosis related genes, and discuss the glucose toxicity and its molecular mechanism. Methods: Apoptosis percentages of primary rat islet cells and βTc3 cells cultured with high concentration glucose medium were measured by TUNEL method, mRNA expressions of bcl-2 and bax of cultured.rat islet cells and mouse βTc3 cells were detected by QRT-PCR. mRNA expressions of bcl-2 and bax of low dosage streptozotocin (STZ) diabetic rat islet cells were measured by QRT-PCR. Results: Apoptosis percentages of islet cells and βTc3 cells increased significantly in high concentration glucose cultured medium, mRNA expression of apoptosis-induced gene bax increased significantly and that of apoptosis-resistant gene bcl-2 decreased significantly in the islet cell apoptosis process, and bd-2Poax ratio decreased significantly. The same results were obtained in the study of apoptosis related gene of diabetic rat islet cells by QRT-PCR. Conclusion: High concentration glucose may aggravate low dosage (STZ) diabetes by increasing islet cell apoptosis, and the change of bcl-2/bax mRNA expression ratio may play an important role in this process.
出处 《天津医药》 CAS 北大核心 2006年第3期176-179,共4页 Tianjin Medical Journal
基金 天津市自然科学基金资助课题(项目编号:983702411 043607911)
关键词 胰岛 细胞 葡萄糖 细胞凋亡 基因表达 islets of langerhans cells glucose apoptosis gene expression
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参考文献5

  • 1Delaney CA, Pavlovic D, Hoorens A, et al. Cytokines induce deoxyribonucleic acid strand breaks and apoptosis in human pancreatic islet cells. Endocrinology, 1997, 138:2610-2614
  • 2Shimabukuro M, Zhou YT, Levi M, et al. Fatty acid-induced β cell apoptosis: a linker between the obesity and diabetes. PNAS USA,1998, 95:2498-2508
  • 3Saafi EL, Konarkowska B, Zhang S, et al, Ultrastructural evidence that apoptosis is the mechanism by which human amylin evokes death in R1Nm 5 F pancreatic islet beta-cells. Cell Biol Int, 2001,25:339-350
  • 4Lupi R, Dotta F, Marsella L, et al. Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets: evidence that beta-cell death is caspase mediated, partially dependent on eeramide pathway and Bcl-2 redulated. Diabetes,2002, 51:1437-1442
  • 5Thomas D, Yang H, Boffa DJ, et al. Proapoptotic bax is hyperexpressed in isolated human islets compared with antiapoptotic Bcl-2.Transplantation, 2002, 74:1489-1496

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