【摘要】：目的研究抑制多聚二磷酸腺苷核糖多聚酶-1(poly ADP-ribose polymerase-1,PARP-1)是否能緩解/逆轉(zhuǎn)細(xì)顆粒物(PM2.5)誘導(dǎo)的炎癥反應(yīng)。方法以不同質(zhì)量濃度(0~1 000μg/mL)PM2.5處理正常人支氣管上皮細(xì)胞(human bronchial epithelium cell line,HBE細(xì)胞)24h,臺(tái)盼藍(lán)拒染法測(cè)定細(xì)胞活力,采用200、400、600μg/mL PM2.5進(jìn)行后續(xù)實(shí)驗(yàn);設(shè)PM2.5(600μg/mL)單處理組、PARP-1抑制劑4-氨基-1,8-萘二胺(4-AN)(10μg/mL)單處理組、4-AN+PM2.5組、溶劑(DMSO)對(duì)照組,免疫印跡法檢測(cè)PARP-1、核因子κ-B(NF-κB)的p65亞基和誘導(dǎo)型一氧化氮合酶(iNOS)表達(dá)水平,硝酸酶還原法檢測(cè)一氧化氮(nitric oxide,NO)水平。結(jié)果 PM2.5 200、400、600μg/mL單獨(dú)處理HBE細(xì)胞時(shí),細(xì)胞存活率隨著PM2.5質(zhì)量濃度增高而下降,PARP-1、p65核轉(zhuǎn)位、iNOS和NO水平升高,400、600μg/mL PM2.5處理組與DMSO對(duì)照組比較,差異有統(tǒng)計(jì)學(xué)意義(P0.05);4-AN預(yù)處理可拮抗PM2.5誘導(dǎo)的PARP-1表達(dá)與p65核轉(zhuǎn)位升高,同時(shí)炎癥介質(zhì)NO與催化合成NO的iNOS水平顯著下降(與PM2.5單處理組比較,差異有統(tǒng)計(jì)學(xué)意義,P0.05),并恢復(fù)至正常水平(與4-AN單處理組和對(duì)照組比較差異無統(tǒng)計(jì)學(xué)意義,P0.05)。結(jié)論抑制PARP-1可以明顯緩解PM2.5對(duì)HBE細(xì)胞的致炎作用,其機(jī)制與下調(diào)NF-κB核轉(zhuǎn)位進(jìn)而阻斷炎癥介質(zhì)表達(dá)有關(guān)。
[Abstract]:Objective to investigate whether inhibiting poly ADP-ribose polymerase-1 (PARP-1) can alleviate / reverse the inflammatory response induced by fine particles (PM2.5). Methods the normal human bronchial epithelial cells (human bronchial epithelium cell lineage cells were treated with different concentration (0 000 渭 g/mL) PM2.5 for 24 h. The viability of the cells was determined by trypan blue exclusion method. 200400600 渭 g/mL PM2.5 was used for the follow-up experiment. The expression of p65 subunit of nuclear factor- 魏 B (NF- 魏 B), p65 subunit of nuclear factor- 魏 B (NF- 魏 B) and inducible nitric oxide synthase (iNOS) were detected by PM2.5 (600 渭 g/mL) single treatment group, 4-an PM2.5 group (10 渭 g/mL) single treatment group and solvent (DMSO) control group. Nitric oxide (no) levels were measured by nitrate reduction method. Results when HBE cells were treated with PM2.5 200400600 渭 g/mL alone, the survival rate of HBE cells decreased with the increase of PM2.5 concentration. The difference was statistically significant (P0.05) that pretreatment with 4-an could antagonize the increase of PARP-1 expression and p65 nuclear translocation induced by PM2.5, while the level of no and the iNOS of catalytic synthesis of no were significantly decreased (compared with PM2.5 single treatment group). The difference was statistically significant (P0.05), and returned to the normal level (compared with 4-AN single treatment group and control group, there was no significant difference (P0.05). Conclusion inhibition of PARP-1 can significantly alleviate the inflammatory effect of PM2.5 on HBE cells, and its mechanism is related to down-regulation of nuclear translocation of NF- 魏 B and blocking the expression of inflammatory mediators.
【作者單位】： 四川大學(xué)華西公共衛(wèi)生學(xué)院環(huán)境衛(wèi)生與職業(yè)醫(yī)學(xué)系;
【基金】：國(guó)家自然科學(xué)基金(No.81372945)資助
【分類號(hào)】：R56

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