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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(0.25mmol/L软脂酸+0.5 mmol/L油酸)、山萘酚组(50μmol/L)、脂肪酸+山萘酚组、PARP-1抑制剂(8μmol/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1h,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。
Objective To investigate the protective effect of kaempferol on fatty acid-induced islet endothelial dysfunction and the effect of poly (ADP-ribose) polymerase 1 (PARP-1). Methods Mouse islet microvascular endothelium MS-1 cells were divided into normal control group, DMSO control group, fatty acid group (0.25 mmol / L palmitate + 0.5 mmol / L oleic acid), mountain The activity of cell viability in each group was measured by the same method. The activities of NF-κB, NF-κB, NF-kappa, PPARα, , The level of apoptosis, the content of nitric oxide (NO), nitric oxide synthase (NOS) and oxidative stress. Results After fatty acid treatment, the survival rate of MS-1 cells decreased and the apoptosis rate increased (P <0.05). Meanwhile, fatty acids also increased intracellular NO content and increased total NOS (tNOS) and inducible NOS iNOS and cNOS (P <0.05). The contents of malondialdehyde (MDA), lipid peroxidation products (GSH) and superoxide dismutase (SOD) ) (P <0.05), and increased the mRNA and protein expressions of PARP-1, iNOS and cNOS (P <0.05). However, the levels of each index were improved after intervention with kaempferol (P <0.05). Furthermore, the antagonistic effect of kaempferol on fatty acids was more obvious with BYK204165 PARP-1 inhibitor pretreatment for 1 h. The detection indexes Compared with the normal control group, there was no significant difference (P> 0.05). Conclusions Fatty acids can directly induce endothelial dysfunction of islets, and kaempferol can antagonize the fatty acid toxicity. Inhibition of PARP-1 expression enhances the protective effect of kaempferol.