中文摘要：

目的观察高脂状态下肺泡Ⅱ型上皮细胞（Alveolar typeⅡepithelial cells,ATⅡ）株A549细胞的脂质蓄积,并探讨炎症对高脂状态下A549细胞脂质蓄积的影响及可能的作用机制。方法将A549细胞分为4组：对照组（不加药物）、高脂组（100μg/ml LDL）、炎症组（300 ng/ml LPS）、联合处理组（100μg/ml LDL＋300 ng/ml LPS）,处理24 h后,油红O染色观察各组细胞内脂质蓄积情况;Real-time PCR检测固醇调节元件结蛋白2（Sterol regulatory elememnt binding proteins 2,SREBP2）、HMGCoA（3-Hydroxy-3-methlglutary 1 coezyme A）还原酶和低密度脂蛋白受体（Low-density lipoprotein receptor,LDLr）基因mRNA转录水平;Western blot法检测SREBP2、LDLr和三磷酸腺酐结合盒转运体A1（ATP-binding cassette sub-family A member 1,ABCA1）蛋白表达水平。结果联合处理组细胞内脂质蓄积较对照组、高脂组及炎症组严重;与对照组相比,高脂组的SREBP2、HMGCoA还原酶、LDLr基因mRNA转录水平反馈性下调（0.54±0.09）、（0.51±0.06）及（0.34±0.06）倍（P〈0.05）;联合处理组各基因mRNA转录水平下调程度低于高脂组;SREBP2及LDLr蛋白表达水平的变化趋势与基因转录水平基本一致;与对照组相比,高脂组ABCA1蛋白的表达反馈性上调（2.78±0.38）倍（P〈0.01）;联合处理组ABCA1蛋白表达上调无高脂组明显。结论炎症可加重高脂状态下肺泡Ⅱ型上皮细胞内的脂质蓄积,其机制可能与炎症干扰SREBP2-LDLr/HMGCoA还原酶通路介导的细胞内脂质稳态有关。

英文摘要：

Objective To observe the lipid accumulation in alveolar type Ⅱ epithelial cells（ATⅡ） A549 under high lipid condition and investigate the effect of inflammation on the accumulation as well as the possible mechanism.Methods A549 cells were divided into four groups.The cells in high lipid,inflammation and combined treatment groups were treated with 100 μg / ml LDL,300 ng / ml LPS and 100 μg / ml LDL ＋ 300 ng / ml respectively,while those in control group were untreated.The lipid accumulation in cells were observed by oil red staining 24 h after treatment,while the transcription levels of sterol regulatory element binding protein 2（SREBP 2）,3-Hydroxy-3-methlglutary 1 coezyme A（HMGCoA） reductase and low-density lipoprotein receptor（LDLr） mRNAs by real-time PCR,and expression levels of SREBP2,LDLr and ATP-binding cassette sub-family A member 1（ABCA1） by Western blot.Results The lipid accumulation in cells in combined treatment group was severer than those in other three groups.Compared with those in control group,the transcription of SREBP2,HMGCoA reductase and LDLr mRNAs in high lipid group decreased by（0.54 ± 0.09）,（0.51 ± 0.06） and（0.34 ± 0.06） folds respectively（P 0.05）.However,the down-regulation levels of mRNAs of various genes in combined treatment group were lower than those in high lipid group.The changing tendencies of SREBP2 and LDLr protein expression levels were basically consistent with those of transcription levels of the corresponding genes.The ABCA1 protein expression level in high lipid group increased by（2.78 ± 0.38） folds as compared with that in control group,However,the up-regulation level of ABCA1 expression in combined treatment group was lower than that in high lipid group.Conclusion Inflammation exacerbates lipid accumulation in alveolar type Ⅱ epithelial cells partly due to the disruption of SREBP2-LDLr / HMGCoA reductase pathway-mediated intracellular lipid homeostasis.