文章摘要
张 娟,赵 原,赵晓宏,周庆元,李晓苗.PTEN参与小檗碱保护脂毒性损伤的胰岛βTC3细胞[J].,2017,17(5):810-814
PTEN参与小檗碱保护脂毒性损伤的胰岛βTC3细胞
PTEN Gene Participated in Protective Effects of Berberine on Lipoapoptosis in Pancreatic βTC3 Cells
投稿时间:2016-03-31  修订日期:2016-04-14
DOI:10.13241/j.cnki.pmb.2017.05.003
中文关键词: 小檗碱  棕榈酸  胰岛βTC3细胞  胰岛素分泌  PTEN
英文关键词: Berberine  Palmic acid  Pancreatic βTC3 cells  Insulin secretion  PTEN
基金项目:国家自然科学基金项目(81573746);陕西省卫计委2014课题(2014D67)
作者单位E-mail
张 娟 第四军医大学西京医院内分泌代谢科 陕西 西安710032三二〇一医院内分泌科 陕西 汉中723000 zhangjmao@163.com 
赵 原 第四军医大学药剂学教研室 陕西 西安 710032  
赵晓宏 三二〇一医院内分泌科 陕西 汉中723000  
周庆元 三二〇一医院内分泌科 陕西 汉中723000  
李晓苗 第四军医大学西京医院内分泌代谢科 陕西 西安710032  
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中文摘要:
      摘要 目的:探讨小檗碱保护棕榈酸诱导的胰岛βTC3细胞的可能机制,观察PTEN是否参与该过程,以及小檗碱对胰岛素分泌的影响。方法:用1.0 mmol/L棕榈酸制作胰岛βTC3细胞脂毒性损伤模型,给予小檗碱干预;放射免疫法检测胰岛素分泌,West- ern blot法进行PTEN、p-AKT、AKT、Bcl-2、Bax、活性Caspase3蛋白的检测。实验分3大组(对照组、棕榈酸组、棕榈酸+小檗碱治疗组),棕榈酸分别作用3个时间段(24、48、72 h)。结果:①放射免疫法胰岛素分泌测定结果显示:β细胞暴露于棕榈酸24 h后,5.6、16.7 mmol/L葡萄糖刺激的胰岛素分泌均较正常对照组显著减少(P<0.01);添加小檗碱干预后胰岛素分泌较棕榈酸组回升,但较对照组减少(P均<0.01)。②在棕榈酸处理的3个时间段内,与对照组相比,棕榈酸组的PTEN、Bax、Active-Caspase3蛋白表达水平显著升高,p-AKT、Bcl-2蛋白水平下降;小檗碱干预后PTEN、Bax蛋白表达水平下降,p-AKT、Bcl-2蛋白水平提高(P均<0.01)。结论:小檗碱可改善棕榈酸引起的胰岛素分泌减少,抑制脂毒性诱导的PTEN表达增加,减少促凋亡基因Bax、Active-Cas- pase3表达,并增加抑凋亡基因Bcl-2基因表达及AKT的活化,从而拮抗棕榈酸诱导的β细胞凋亡,保护?茁细胞功能。
英文摘要:
      ABSTRACT Objective: To evaluate the protective effect of berberine on pancreatic βTC3 cells lipoapoptosis induced by free fatty acids, investigated the role of PTEN/AKT signaling in berberine involved beta cell protection. To explore the anti-diabetic effects of berberine and its influence on inslin secretion. Methods: The basal and glucose stimulated insulin secretion capability of βTC3 cells were evaluated when exposed to FFAs with or without berberine by Radioimmunoassay. The expression of PTEN, AKT, p-AKT and apoptosis related proteins Bax, Bcl-2 and Active-Caspase3 were detected by western blotting in βTC3 cells when exposed to FFAs with or without berberine. Results: Berberine substantially facilitated the basal and glucose stimulated insulin secretion of beta cells in high FFAs condi- tion. Western blot revealed that the phosphorylation of AKT and Bcl-2 was markedly decreased under lipid stress but was elevated when treated with berberine. Moreover, FFAs could up-regulate the expression levels of PTEN, Bax, and Active-Caspase3, but down-regulate the expression levels of p-AKT and Bcl-2 in beta cells, which were canceled by the addition of berberine. Conclusion: Berberine observ- ably inhibited the apoptosis, elevated proliferation and the basal and glucose stimulated insulin secretion of beta cells in high FFAs condi- tion. Furthermore, the protective action of berberine was probability mediated by activation of PTEN/AKT, which was accompanied by the down-regulation of Bax, Active-Caspase3 and up-regulation of p-AKT and Bcl-2 expressions.
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