| 摘要: |
| 目的 探讨山萘酚对脂肪酸诱导的胰岛微血管内皮功能损伤的保护效应及多聚腺苷二磷酸核糖聚合酶1(PARP-1)的作用。 方法 以小鼠胰岛微血管内皮MS-1细胞为研究对象, 将细胞分为正常对照组、溶剂(DMSO)对照组、脂肪酸组(0.25 mmol/L软脂酸+0.5 mmol/L油酸)、山萘酚组(50 μmol/L)、脂肪酸+山萘酚组、PARP-1抑制剂(8 μmol/L BYK204165)+脂肪酸组和PARP-1抑制剂+脂肪酸+山萘酚组, 分别检测各组细胞活力、凋亡水平、一氧化氮(NO)、一氧化氮合酶(NOS)及氧化应激相关指标的改变。 结果 脂肪酸处理后, MS-1细胞存活率下降, 细胞凋亡率升高(P<0.05);同时, 脂肪酸也增加了细胞内NO的含量, 升高了总NOS(tNOS)、诱导型NOS(iNOS)和结构型NOS(cNOS)的活性(P<0.05);促使脂质过氧化产物丙二醛(MDA)含量增加, 抗氧化物质谷胱甘肽(GSH)和超氧化物歧化酶(SOD)的水平下降(P<0.05);并增强了PARP-1、iNOS和cNOS的mRNA和蛋白表达水平(P<0.05)。而山萘酚干预后, 各项指标的水平均得以改善(P<0.05);而且, 利用PARP-1抑制剂BYK204165预处理1 h, 山萘酚对脂肪酸的拮抗效应更为显著, 各项检测指标与正常对照组比较差异无统计学意义(P>0.05)。 结论 脂肪酸可直接引起胰岛微血管内皮功能损伤, 而山萘酚具有拮抗脂肪酸毒性的作用, 且抑制PARP-1的表达水平能增强山萘酚的保护效应。 |
| 关键词: 山萘酚 脂肪酸类 胰岛 微血管 血管内皮 聚ADP核糖聚合酶类 |
| DOI：10.16781/j.0258-879x.2016.03.0295 |
| 投稿时间：2015-09-23修订日期：2015-10-16 |
| 基金项目: |
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| Protective effects of kaempferol against fatty acid-induced islet microvessel endothelial function injury and the role of poly(ADP-ribose) polymerases-1 |
| TIAN Mi1,2,LEI Qi1,YAN Yun-sheng3,LI Long-kun2* |
(1. Chongqing Radio and TV University, Chongqing 400052, China;
2. Key Laboratory of Urology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China;
3. Department of ICU, Chongqing Zhongshan Hospital, Chongqing 400013, China
*Corresponding author) |
| Abstract: |
| Objective To investigate the protective effects of kaempferol against the fatty acid-induced islet microvessel endothelial function injury and the role of poly(ADP-ribose) polymerases-1(PARP-1). Methods Mouse islet microvessel endothelial MS-1 cells were divided into normal control group, solvent (DMSO) group, fatty acid group (0.25 mmol/L palmitic acid+0.5 mmol/L oleic acid), kaempferol group (50 μmol/L), fatty acid+kaempferol group, PARP-1 inhibitor (8 μmol/L BYK204165)+fatty acid group and PARP-1 inhibitors+fatty acid+kaempferol group. The changes of cell viability, apoptosis, nitric oxide (NO), nitric oxide synthase (NOS)and oxidative stress related indicators were examined in each group. Results After treatment with fatty acid, the survival rate of MS-1 cells was significantly decreased and the apoptosis rate was significantly increased (P<0.05); meanwhile, fatty acids also increased NO production and promoted the activities of the total NOS (tNOS), inducible NOS (iNOS) and constitutive NOS (cNOS) in the MS-1 cells (P<0.05). Treatment with fatty acid also significantly increased the lipid peroxidation products-malondialdehyde (MDA), while significantly decreased the levels of antioxidants, glutathione (GSH) and superoxide dismutase (SOD) (P<0.05); and it also increased the mRNA and protein expression of PARP-1, iNOS and cNOS (P<0.05). Kaempferol significantly attenuated the toxic effects of fatty acids concerning all the detected indicators (P<0.05). Moreover, pretreatment with PARP-1 inhibitor (BYK204165) for 1 h markedly enhanced the protective effects of kaempferol, and all the detected parameters were similar to those of the control group(P>0.05). Conclusion Fatty acid can directly trigger islet microvessel endothelial function injury, and kaempferol shows a protective effect against the toxicity of fatty acid. Inhibition of PARP-1 can significantly promote the protective effects of kaempferol. |
| Key words: kaempferol fatty acids islets of langerhans microvessels vascular endothelium poly (ADP-ribose) polymerases |
