聚(ADP-核糖)聚合酶1在游离脂肪酸诱导胰岛细胞凋亡中的作用

Effect of Poly [ADP-ribos] polymerase (PARP-1) on the apoptosis of islet cell induced by free fatty acid

目的研究RIN-m5F胰岛细胞在游离脂肪酸(FFA)作用下聚(ADP-核糖)聚合酶1(PARP-1)基因的表达。方法细胞经FFA处理后,检测其胰岛素分泌水平、细胞内PARP-1 mRNA和蛋白的表达以及细胞凋亡。结果经软脂酸(PA)处理后细胞胰岛素分泌水平明显降低(P<0.01),而油酸(OA)明显抑制了PA对胰岛细胞功能的影响;细胞经PA处理后,PARP-1表达显著升高(P<0.01);而PA+OA组PARP-1表达较PA组明显降低(P<0.01)。结论不饱和脂肪酸OA在适当条件下能抑制饱和脂肪酸PA所诱导的RIN-m5F胰岛细胞功能损伤及凋亡,此过程可能与PARP-1的表达密切相关。

Objective To explore the effects of PARP-1 on the apoptosis of islet cell induced by free fatty acid. Methods The insulin-secreting RIN-m5F islet cells line were cultured and treated with free fat acid. The level of insulin in the culture medium was measured by RIA. The expression of PARP-1 gene of the cells was detected by RT-PCR and Western-blot, and the cell apoptosis was observed by flow cytometry. Results The insulin secretion of RIN-m5F islet cell decreased significantly when cells were treated with palmitic acid alone （P〈 0. 01）. Simultaneous administration of oleic acid （OA） and PA significantly suppressed the impaired insulin secretion and the PA-induced apoptosis （P〈 0.01）. The expression of PARP-1 was significantly increased when treated with PA （P〈0. 01）, but was significantly decreased when treated with PA q-OA as compared with PA alone （P〈 0.01）. Conelusions The saturatus fatty acids palmitic acid significantly inhibits the insulin secretion capacity, and induces the cell apoptosis, but unsaturated fatty acids could suppress the impaired function induced by palmitic acid in RIN-mSF cell line, and a concurrent alteration of PARP-1 expression suggests that this is a regulatory pathway by which free fatty acid induces the apoptosis of islet cell.