目的 探讨神经调节蛋白4(Nrg4)对2型糖尿病小鼠主动脉内皮细胞凋亡的影响。方法 将C57小鼠分为对照(Vehicle)组、糖尿病(DM)组和Nrg4干预糖尿病小鼠(Nrg4)组。Nrg4组腹腔注射Nrg4重组蛋白(100 μg/kg,3次/周),Vehicle组与DM组小鼠注射等量生理盐水,干预周期均为8周。实验结束后,TUNEL荧光染色检测主动脉内皮细胞凋亡,Western blot检测主动脉内皮组织凋亡相关蛋白Bax、Bcl-2及Cleaved-caspase 3的表达。结果 与Vehicle组相比,DM组主动脉内皮细胞凋亡率明显升高[(33.0±5.4)% vs.(20.5±3.0)%;P＜0.05],促凋亡蛋白Bax与凋亡执行蛋白Cleaved-caspase 3表达明显增多,抗凋亡蛋白Bcl-2表达显著减少(P＜0.05);而Nrg4干预明显抑制糖尿病小鼠主动脉内皮细胞凋亡[(19.2±3.8)% vs.(33.0±5.4)%;P＜0.05],降低Bax与Cleaved-caspase 3的表达并促进Bcl-2表达(P＜0.05)。结论 Nrg4干预能缓解2型糖尿病小鼠主动脉内皮细胞凋亡。
Abstract
Objective To investigate the effects of neuregulin 4 (Nrg4) on the apoptosis of endothelial cells in type 2 diabetic mice. Methods C57 mice were randomly divided into Vehicle group, diabetes mellites (DM) group and Nrg4 administration group (NRG4). Nrg4 group was intraperitoneally (i.p.) injected with Nrg4 recombinant protein (100 μg/kg, 3 times/week) and the same volume of saline was i.p. injected in the other two groups for 8 weeks. After the experiment, TUNEL staining was used to evaluate apoptotic rate of endothelial cells, and Western blot was used to investigate the protein levels of apoptosis-associated proteins. Results Compared with Vehicle group, DM significantly promoted cell apoptosis [(33.0±5.4)% vs. (20.5±3.0)%;P<0.05], increased Bax and cleaved-caspase 3 expression, and decreased Bcl-2 expression (P<0.05), while Nrg4 administration obviously decreased endothelial apoptosis [(19.2±3.8) % vs. (33.0±5.4) %; P<0.05], decreased Bax and cleaved-caspase 3 expression, and increased Bcl-2 expression (P<0.05). Conclusions Nrg4 administration can alleviate the apoptosis of aortic endothelial cells in type 2 diabetic mice.
关键词
神经调节蛋白4 /
糖尿病 /
内皮细胞 /
细胞凋亡
Key words
neuregulin 4 /
diabetes mellitus /
endothelial cell /
cell apoptosis
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