糖脂毒性对肥胖大鼠β细胞功能和凋亡的影响研究

发布时间：2018-08-13 17:52

【摘要】：目的探讨葡萄糖和游离脂肪酸(FFA)联合作用对胰岛β细胞功能与凋亡的影响及病理生理机制。方法Wistar大鼠采用高脂饲料喂养制造胰岛素抵抗模型,取造模成功的肥胖胰岛素抵抗模型大鼠分为4个亚组,生理盐水组(OB-NS组,n=7)、高葡萄糖组(OB-GS组,n=9)、高游离脂肪酸组(OB-FFA组,n=8)和高糖高脂肪酸组(OBFG组,n=9)。另取5只Wistar大鼠采用普通饲料喂养作为正常对照组。采用比色法检测FFA和β-羟丁酸(β-HBA)水平,采用静脉葡萄糖耐量试验(IVGTT)评价胰岛β细胞胰岛素分泌功能,免疫组织化学方法检测β细胞胰岛素储备的能力,并应用原位末端标记法(TUNEL)检测凋亡的β细胞。结果肥胖大鼠葡萄糖输注率(GIR)低于正常对照〔(10.82±1.8mg/kg·min)vs.(25.21±1.7mg/kg·min),P0.05〕,提示胰岛素抵抗模型成功建立。OB-FG组大鼠糖负荷后胰岛素分泌达峰时间延后且各时点胰岛素水平明显低于NC组和OB-NS组,差异有统计学意义(P0.05)。糖负荷后5、10、15和20min时,OB-FG组血胰岛素水平也明显较OB-FFA组、OB-GS组降低,胰岛素和血糖比值及胰岛素释放指数也均低于NC组和OB-NS组,差异有统计学意义。免疫组织化学染色示,OB-FG组胰岛素储备在各高脂肥胖亚组中最低,远低于NC组和OB-NS组(P0.01),OB-GS组和OB-FFA组胰岛素储备与OB-NS组比较也有不同程度降低(P0.05)。OB-FG组β细胞凋亡率高于NC组和OB-NS组(P0.01)。结论糖脂联合毒性在引起肥胖大鼠酮体生成显著增加的同时也导致胰岛细胞分泌功能障碍。
[Abstract]:Objective to investigate the effect of glucose and free fatty acid (FFA) on the function and apoptosis of islet 尾 cells and its pathophysiological mechanism. Methods Wistar rats were fed with high fat diet to produce insulin resistance model. The obese insulin resistance model rats were divided into 4 subgroups. Normal saline group (OB-NS group), high glucose group (OB-GS group), high free fatty acid group (OB-FFA group) and high glucose fatty acid group (OBFG group). Another 5 Wistar rats were fed with normal diet as normal control group. The levels of FFA and 尾 -hydroxybutyric acid (尾 -HBA) were detected by colorimetry, insulin secretion function of islet 尾 cells was evaluated by intravenous glucose tolerance test (IVGTT), and the ability of 尾 -cell insulin reserve was detected by immunohistochemical method. Apoptotic 尾-cells were detected by in situ end labeling (TUNEL). Results the glucose infusion rate (GIR) of obese rats was lower than that of normal control (10.82 卤1.8mg/kg min) vs. (25.21 卤1.7mg/kg min) P 0.05), which suggested that the insulin resistance model was established successfully in the OB-FG group, and the peak time of insulin secretion was delayed and the insulin level at each time point was significantly lower than that in NC group and OB-NS group. The difference was statistically significant (P0.05). The serum insulin level in OB-FG group was significantly lower than that in OB-FFA OB-GS group, and the insulin / glucose ratio and insulin release index in OB-FG group were lower than those in NC group and OB-NS group. Immunohistochemical staining showed that the insulin reserve in OB-FG group was the lowest in all high-fat obesity subgroups, which was significantly lower than that in NC group and OB-NS group (P0.01), OB-GS group and OB-FFA group, compared with OB-NS group (P0.05). The 尾 -cell apoptosis rate in OB-FG group was higher than that in NC group and OB-NS group (P0.01). Conclusion combined glycolipid toxicity can significantly increase the formation of ketones in obese rats and also lead to the dysfunction of pancreatic islet cell secretion.
【作者单位】：四川大学华西医院内分泌科;四川大学华西医院内分泌代谢研究室;
【基金】：国家自然科学基金(No.30570874) 四川省科技厅科技支撑计划项目(No.2016SZ0058)资助
【分类号】：R589.2

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