单次大剂量链脲佐菌素诱导的糖尿病模型β细胞凋亡的研究及意义探讨

Single high streptozotocin dose-induced β-cell apoptosis in diabetic model and its significance

目的详细阐述单次大剂量链脲佐菌素(streptozotocin,STZ)诱导的SD大鼠1型糖尿病模型中β细胞凋亡的时相变化。方法 SD大鼠腹腔一次性注射大剂量STZ(65 mg/kg),观察血糖及胰岛素水平的动态变化,在指定时间点处死大鼠,对胰腺行HE染色、免疫荧光染色及TUNEL染色。结果注射STZ后,SD大鼠血糖呈现出一个高-低-高的三相反应,伴随着胰岛素水平低-高-低的变化以及相应的病理学改变。STZ注射后6 h,β细胞凋亡率(由TUNEL染色衡量)大幅度上升,β细胞凋亡较为同步,此后β细胞凋亡率急剧下降,直到STZ注射后48 h,几乎检测不到β细胞的凋亡。结论单次大剂量STZ诱导的SD大鼠1型糖尿病模型β细胞凋亡在病程早期(STZ注射后6 h)即达高峰,且较为同步,相应出现了血糖水平、胰岛素水平以及胰岛病理结构的变化。

Objective To elaborate the phasic change of β-cell apoptosis in single high streptozotocin（STZ） dose-induced type 1 diabetic model of SD rats.Methods A single high STZ dose（65 mg/kg） was injected into the abdominal cavity of SD rats and their blood glucose and insulin levels were measured.The rats were then sacrificed at the indicated time points and their pancreatic tissue was stained with HE,immunofluorescence,and TUNEL,respectively.Results The rats showed the high-low-high blood glucose level accompanying the low-high-low insulin level and corresponding pathological changes after they were injected with STZ.The β-cell apoptosis（measured with TUNEL staining） increased dramatically 6 hours after STZ injection and sharply reduced 48 hours after STZ injection.The Β-cell apoptosis was hardly detected.Conclusion The β-cell apoptosis reaches its peak with corresponding changes in blood glucose and insulin levels and in pathological structure of islet 6 hours after a type 1 diabetic model of SD rats is induced with a single high STZ dose.