摘要
目的探讨小檗碱对胰岛素抵抗大鼠胰岛β细胞凋亡的影响。方法采用高果糖饮食喂养建立大鼠胰岛素抵抗模型,给予小檗碱治疗6周,行口服葡萄糖耐量试验(OGTT)检测空腹胰岛素(Fins),计算胰岛素敏感指数(ISI),分离与纯化胰岛,原位末端核苷酸标记法(TUNEL)检测胰岛β细胞凋亡,免疫组化检测胰岛凋亡相关蛋白ASK1、Caspase-12的表达。结果与正常组比较,胰岛素抵抗大鼠OGTT0、1h血糖升高,Fins增加,ISI降低,血脂紊乱,胰岛β细胞凋亡增加,凋亡相关蛋白ASK1、Caspase-12表达增加;与模型组比较,小檗碱组OGTT0、1h血糖、Fins降低,ISI增加,血脂紊乱改善,胰岛β细胞凋亡减少,凋亡相关蛋白ASK1表达减少,而Caspase-12表达无明显改变。结论小檗碱能改善胰岛素抵抗大鼠的胰岛素抵抗状态,减少胰岛β细胞凋亡,其机制可能与抑制ASK1表达有关。
Objective To explore the effects of berberine on the pancreatic β cell apoptosis in rats with insulin resistance（IR）.Methods IR Wistar rat model was established by feeding with high fructose diet.After 6-week treatment of berberine,oral glucose tolerance test（OGTT） was performed.Then fasting insulin level（Fins） was detected and insulin sensitivity index（ISI） calculated.The islet was isolated and purified.The pancreatic β cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay（TUNEL）.The apoptosis-related protein ASK1 and Caspase-12 expressions were examined by immunohistochemical assay.Results Compared with the normal group,the blood glucose at 0 and 1 h increased,the Fins increased and ISI decreased,the blood lipids were disarranged,the pancreatic β cell apoptosis increased,and ASK1 and Caspase-12 protein expressions increased in IR rats.Compared with the model group,the blood glucose at 0 and 1 h and the Fins decreased,ISI increased,the disarranged blood lipids were improved,the pancreatic β cell apoptosis decreased,and the ASK1 expression decreased,but with no obvious change in the Caspase-12 expressions in the berberine group.Conclusions Berberine could alleviate IR state in IR rats and inhibit pancreatic β cell apoptosis.Its mechanism might be correlated with the inhibition of ASK1 protein expressions.
出处
《中国中西医结合杂志》
CAS
CSCD
北大核心
2011年第10期1383-1388,共6页
Chinese Journal of Integrated Traditional and Western Medicine
基金
国家自然科学基金资助项目(No.30772853)
关键词
小檗碱
胰岛素抵抗
内质网应激
凋亡
berberine
insulin resistance
endoplasmic reticulum stress
apoptosis
