ＰＡＲＰ-１抑制剂在游离脂肪酸诱导胰岛细胞凋亡中的作用

目的:探讨PARP-1抑制剂3-氨基苯酰胺(3-Aminobenzamide,3-AB)在游离脂肪酸棕榈酸诱发的胰岛细胞凋亡和坏死中的作用.方法:常规培养RIN-m5F细胞株,采用四甲基偶氮唑盐(MTY)比色法观察棕榈酸和PARP-1抑制剂3-AB作用后细胞的增殖情况,并用流式细胞术及TUNEL法分析细胞凋亡和坏死.结果:棕榈酸明显抑制RIN-m5F细胞的增殖(P<0.01);低浓度3-AB与棕榈酸共同孵育24 h后细胞的凋亡率和坏死率显著低于棕榈酸单独培养(P<0.01);高浓度3-AB与棕榈酸共同孵育后较棕榈酸单独培养时细胞凋亡率显著性增强(P<0.01).结论:低浓度3-AB能有效抑制棕榈酸所诱导的胰岛细胞株RIN-m5F细胞坏死,缓解细胞凋亡;而高浓度3-AB则促进细胞凋亡.进一步说明了3-AB在棕榈酸所诱导的胰岛细胞凋亡过程中具有双重作用,此可为2型糖尿病的治疗提供一个新的靶点.

Effect of the poly(ADP-ribose) polymerase inhibitor on the apoptosis of islet cell induced by free fatty acid

Objective:To explore the effects of PARP inhibitor(3-Aminobenzamide) on the apoptosis and necrosis of islet cell induced by palmitic acid. Methods:The RIN-m5F cell line was routinely cultured,and MTT method was employed to evaluate the proliferation of the RIN-m5F cell line. Moreover,Flow cytometry and TUNEL method were enrolled to analyze the apoptosis and necrosis of the RIN-m5F cell line. Results:Palmitic acid significantly inhibited the proliferation of the RIN-m5F cell line(P < 0.01).The apoptosis and necrosis of the RIN-m5F cell line treated by lower concentration of 3-Aminobenzamide and palmitic acid were obviously lower than that treated by palmitic acid alone after 24 h(P < 0.01),but the apoptosis was more significantly enhanced when the concentration of 3-Aminobenzamide higher(P < 0.01). Conclusion:Lower concentration of 3-Aminobenzamide could suppress effectively the apoptosis and necrosis of RIN-m5F cell line induced by palmitic acid,but higher concentration of 3-Aminobenzamide alternatively enhanced the apoptotic rate. It was indicated that 3-Aminobenzamide could have positive and negative effect in different concentration on the apoptosis of islet cell induced by palmitic acid and could be served as a novel therapeutic target for type 2 diabetes.