Gan Xiaguang, Wu Qi'nan, Deng Wuquan, Zhang Ling, Chen Bing
Department of Endocrinology, First Affi liated Hospital, Third Military Medical University, Chongqing 400038, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2015 Jan;40(1):6-11. doi: 10.11817/j.issn.1672-7347.2015.01.002.
To explore the effect of high glucose and lipid intervention on islet cell apoptosis through the inhibition of prostate apoptosis response factor-4 (Par-4) expression and the underlying mechanisms.
The mice islet β cells (NIT-1 cells) were randomly divided into a control group, a Par-4 inhibited group, a glucose and fatty acid intervented group and a glucose and fatty acid intervented+Par-4 inhibited group. Cell apoptosis was detected by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL), and the protein expression levels of Par-4 and glucose regulated protein 78 (GRP78) were detected by Western blot.
Compared with the control group [(3.14 ± 1.08)%], the apoptosis rate of islet beta cell [(33.82 ± 3.15)%] in the glucose and fatty acid intervented group was significantly increased accompanied by the dramatically elevated Par-4 and GRP78 expression (both P<0.05). Compared with the glucose and fatty acid intervented group, the apoptosis rate in glucose and fatty acid intervented+Par-4 inhibit group [(18.3 4 ± 2.11)%] was significantly decreased concomitant with the significantly decreased Par-4 and GRP78 expression (both P<0.05).
The glucose and fatty acid-induced apoptosis of mice islet β cells could be improved through the inhibition of Par-4 expression, which might be related to reduction of endoplasmic reticulum stress.
通过抑制前列腺凋亡反应因子4(Par-4)表达来探讨高糖高脂干预对胰岛细胞凋亡的影响及其潜在机制。
将小鼠胰岛β细胞(NIT-1细胞)随机分为对照组、Par-4抑制组、葡萄糖和脂肪酸干预组以及葡萄糖和脂肪酸干预+Par-4抑制组。采用末端脱氧核苷酸转移酶(TdT)介导的dUTP缺口末端标记法(TUNEL)检测细胞凋亡情况,并用蛋白质印迹法检测Par-4和葡萄糖调节蛋白78(GRP78)的蛋白表达水平。
与对照组[(3.14±1.08)%]相比,葡萄糖和脂肪酸干预组胰岛β细胞凋亡率[(33.82±3.15)%]显著升高,同时Par-4和GRP78表达显著上调(均P<0.05)。与葡萄糖和脂肪酸干预组相比,葡萄糖和脂肪酸干预+Par-4抑制组凋亡率[(18.34±2.11)%]显著降低,Par-4和GRP78表达也显著下降(均P<0.05)。
抑制Par-4表达可改善葡萄糖和脂肪酸诱导的小鼠胰岛β细胞凋亡,这可能与内质网应激减轻有关。