發(fā)布時(shí)間：2018-03-07 23:06

  本文選題：阿托伐他汀　切入點(diǎn)：炎癥應(yīng)激　出處：《中國(guó)臨床藥理學(xué)雜志》2017年09期 　論文類型：期刊論文

【摘要】：目的研究阿托伐他汀在炎癥狀態(tài)下對(duì)人肝癌細(xì)胞株Hep G2細(xì)胞氧化應(yīng)激和脂質(zhì)積聚的影響。方法將普通Hep G2細(xì)胞分為為3組:正常組、模型組[用100 ng·m L~(-1)腫瘤壞死因子(TNF-α)處理]及實(shí)驗(yàn)組(用100 ng·m L~(-1)TNF-α+10μmol·L~(-1)阿托伐他汀處理),3組同時(shí)負(fù)荷100μg·m L~(-1)低密度脂蛋白(LDL),處理時(shí)間24 h。用油紅O染色測(cè)定細(xì)胞內(nèi)脂質(zhì)含量;以熒光定量聚合酶鏈?zhǔn)椒磻?yīng)和免疫印跡法分別檢測(cè)Hep G2細(xì)胞脂肪酸合酶(FAS)、乙酰輔酶A羧化酶(ACC)和固醇調(diào)節(jié)元件結(jié)合蛋白1(SREBP1)的基因和SREBP1蛋白表達(dá);以二氯二氫熒光素-乙酰乙酸酯(DCFH-DA)熒光探針染色檢測(cè)Hep G2細(xì)胞內(nèi)活性氧化產(chǎn)物(ROS)的含量;以比色法檢測(cè)Hep G2細(xì)胞過氧化氫(H2O2)和丙二醛(MDA)的含量。結(jié)果正常組與模型組SREBP1蛋白灰度值分別為1.01±0.001,1.61±0.34,這2組的SREBP1 mRNA水平分別為1.01±0.16,3.61±0.39,這2組的FAS的mRNA水平分別是1.03±0.32,1.99±0.36,這2組的ACC的mRNA水平分別是0.95±0.29,2.37±0.52。與正常組相比,模型組的細(xì)胞FAS、ACC、SREBP1的基因和SREBP1的蛋白表達(dá)明顯增加,差異均有統(tǒng)計(jì)學(xué)意義(均P0.05)。與模型組相比,實(shí)驗(yàn)組的Hep G2FAS、ACC、SREBP1的基因和SREBP1的蛋白灰度值分別是2.95±0.92,3.99±1.16,2.85±0.91,2.94±0.65,實(shí)驗(yàn)組的Hep G2 FAS、ACC、SREBP1的基因和SREBP1的蛋白表達(dá)明顯增加,差異均有統(tǒng)計(jì)學(xué)意義(均P0.05)。表明在炎癥狀態(tài)下,阿托伐他汀進(jìn)一步加重了Hep G2細(xì)胞內(nèi)脂質(zhì)的沉積。正常組、模型組與實(shí)驗(yàn)組的細(xì)胞ROS含量(以熒光強(qiáng)度代表)分別為1.00±0.20,1.77±0.25,3.20±0.53;正常組、模型組與實(shí)驗(yàn)組的H2O2含量分別為(2.30±0.31),(4.32±0.77),(5.31±0.75)nmol·mg~(-1);這2組的MDA含量分別為(0.78±0.22),(1.86±0.23),(3.43±1.15)nmol·mg~(-1),與正常組比較,模型組差異均有統(tǒng)計(jì)學(xué)意義(均P0.05);與模型組比較,實(shí)驗(yàn)組差異均有統(tǒng)計(jì)學(xué)意義(均P0.05)。結(jié)論在炎癥狀態(tài)下,阿托伐他汀誘導(dǎo)Hep G2細(xì)胞氧化應(yīng)激,激活SREBP1/FAS/ACC通路,加重細(xì)胞內(nèi)脂質(zhì)積聚。
[Abstract]:Objective to study the effects of Atto vastatin on oxidative stress and lipid accumulation in Hep G2 cells under inflammatory condition. Model group [100ng 路mL ~ (-1)) TNF- 偽] and experimental group (100ng 路mL ~ (-1) TNF- 偽 10 渭 mol 路L ~ (-1)) Atto vastatin were treated with 100 渭 g 路m ~ (-1) mol 路L ~ (-1) low density lipoprotein (LDL). Fluorescence quantitative polymerase chain reaction (FQ-PCR) and Western blot were used to detect the gene and SREBP1 expression of fatty acid synthase (FASN), acetyl coenzyme A carboxylase (Hep) and steroid regulatory element binding protein (SSREBP1) in Hep G2 cells. The content of reactive oxidation product (Ros) in Hep G2 cells was detected by DCFH-DAA fluorescence probe staining. Results the grayscale values of SREBP1 protein in normal group and model group were 1.01 鹵0.001 鹵0.34 and 1.01 鹵0.16 鹵3.61 鹵0.39, respectively. The mRNA level of FAS in these two groups was 1.03 鹵0.32 鹵0.36, respectively. The mRNA levels of ACC were 0.95 鹵0.29 and 2.37 鹵0.52, respectively. In the model group, the gene expression of FASA ACC-SREBP1 and the protein expression of SREBP1 were significantly increased (all P 0.05), compared with the model group, the expression of FASACC-SREBP1 was significantly higher than that of the model group (P < 0.05). The grayscale values of Hep G2FASA ACC-SREBP1 gene and SREBP1 protein were 2.95 鹵0.92 鹵1.16 ~ 3.99 鹵0.91 鹵2.94 鹵0.65, respectively. The expression of Hep G2FASA ACC-SREBP1 gene and SREBP1 protein in the experimental group were significantly increased (all P0.05), indicating that the expression of Hep G2FAS-ACC-SREBP1 protein was significantly higher in the experimental group than that in the control group (P0.05). Atto vastatin further aggravated lipid deposition in Hep G2 cells. The ROS content in normal group, model group and experimental group (represented by fluorescence intensity) was 1.00 鹵0.20 鹵0.253.20 鹵0.53, respectively. The content of H _ 2O _ 2 in the model group and the experimental group was 2.30 鹵0.31 鹵0.77 nmol 路mg ~ (-1), respectively, and the MDA content in the two groups was 0.78 鹵0.22 nmol 路mg ~ (-1) and 1.86 鹵0.23 ~ (1) nmol 路mg ~ (-1), respectively. There were significant differences between the model group and the normal group (P 0.05). Conclusion under the condition of inflammation, Atto vastatin induces oxidative stress in Hep G2 cells, activates SREBP1/FAS/ACC pathway and exacerbates intracellular lipid accumulation.
【作者單位】： 重慶醫(yī)科大學(xué)脂糖代謝性疾病重慶市重點(diǎn)實(shí)驗(yàn)室;
【基金】：國(guó)家自然科學(xué)基金資助項(xiàng)目(31540029) 重慶市第七批市科技計(jì)劃基金資助項(xiàng)目(cstc2016jcyj A0545)
【分類號(hào)】：R96

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