摘要
目的 观察血糖波动对在体大鼠胰岛β细胞凋亡的影响以及核因子（NF）-кB在其中的作用.方法 通过高脂饲料及注射小剂量链脲佐菌素（STZ）20mg/kg的方法制造糖尿病（DM）大鼠模型,小剂量高糖（25%的葡萄糖溶液10mg/g体重）每日3次腹腔注射制造持续高糖（SHG）组模型,在SHG组基础上高糖注射后0.5h皮下注射诺和锐1U/100g,造成每日血糖波动3次的血糖波动（IHG）大鼠模型.根据血糖、血糖波动分正常（N）组、DM组、SHG组、IHG组4组.实验14d结束并检测胰腺组织氧化应激指标丙二醛（MDA）、超氧化物歧化酶（SOD）,酶标记免疫吸附测定（ELISA）方法检测炎症指标肿瘤坏死因子（TNF）-α、环氧酶（COX）-2以及凋亡基因Bax、Bcl-2,NF-кB等.原位末端转移酶标记技术（TUNEL）法观察胰岛细胞凋亡指数.结果 DM组、SHG组、IHG组较N组MDA 、TNF-α、COX-2、Bax含量升高,SOD、Bcl-2含量减少,NF-кB含量升高,胰岛细胞凋亡指数增多.与DM组比较,SHG组和IHG组MDA、Bax、NF-кB含量升高以及胰岛细胞凋亡指数升高.与SHG组比较,IHG组NF-кB含量最高、Bcl-2/Bax值最低,胰岛细胞凋亡指数最高.偏相关分析提示,Bcl-2/Bax与NF-κB之间具有相关性（r=-0.239,P＜0.05）.结论 血糖波动明显增加β胰岛细胞凋亡,可能与血糖波动增加氧化应激、炎症反应,激活并放大了NF-кB活性,NF-кB通过调节炎症及下游凋亡基因而促进胰岛细胞凋亡.
Objective To investigate the effects of blood glucose fluctuation on NF- κB expression and apoptosis of islet β cells in rats. Methods Diabetes mellitus （DM） was induced by injection of STZ （20 mg/kg） and high fat feed in rats; The sus- taining hyperglycemia （SHG） model was induced by intraperitoneal injection of 25% glucose 3 times/day, then subcutaneous in- jection of novorapid （1U/100g） was given to induce the glucose fluctuation （3 times/day） model （IHG）. The rats were divided into 4 groups： normal group, DM group, SHG group, and IHG group. Two weeks after models were set, the pancreas were taken from animals of each group. The MDA, SOD levels in pancreatic tissue were measured; TNF- α, COX-2, BAX, BCL-2 and NF- κB were detected by ELISA methods; the apoptosis of islet β cells was detected by TUNEL method. Results Compared to normal group, MDA, TNF-α, COX-2, BAX, NF- κB levels and apoptosis index of islet β cells were increased in DM,SHG and IHG groups, while SOD and BCL-2 decreased. Compared to DM group, MDA, BAX, NF- κB levels and apoptosis index of islet β cells were increased in SHG and IHG groups. Compare to SHG group, NF- κB and apoptosis index of islet β cell were higher and BCL-2/Bax was lower in IHG group. BCL-2/Bax was negatively correlated with NF- κB （r=-0.239,P〈0.05）. Conclusion Glucose fluctuation may induce apoptosis of islet β cells, which might be associated with oxidative stress, inflammatory reaction and resulting activation of NF- κB.
出处
《浙江医学》
CAS
2012年第9期708-711,共4页
Zhejiang Medical Journal
基金
浙江省教育厅资助项目（N20100138）
浙江省自然科学基金（Y2110738）
