Suppression of IRE1α Attenuated the Fatty Degeneration in Parenteral Nutrition-Related Liver Disease (PNALD) Cell Model
Suppression of IRE1α Attenuated the Fatty Degeneration in Parenteral Nutrition-Related Liver Disease (PNALD) Cell Model
复制标题
IRE1α 的抑制减轻了肠外营养相关肝病 (PNALD) 细胞模型中的脂肪变性
DOI：
10.1155/2020/7517540
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发表时间：
2020-02-03
影响因子：
2
通讯作者：
Zhu，Xiaoli
中科院分区：
文献类型：
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作者：
Cui，Ningxun;Cui，Mingling;Zhu，Xiaoli
目的建立大鼠正常肝细胞肠外营养相关性肝病模型，探讨内质网应激相关的IRE1α信号在肠外营养相关性肝病发病过程中的作用。通过油红O染色和生化指标的分析，进一步证实了PNALD细胞疾病模型。结果油红O染色结果表明，pNALD成功地在BRL细胞中建立，CCK-8实验结果表明，0.60%的SO对α有较好的诱导作用，且对细胞的毒性较小，进一步应用于本实验。此外，SO组大鼠血清总胆红素(TBIL)、总胆红素(DBIL)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)等生化指标也明显高于正常对照组。IRE1α基因敲除后，细胞对SO的耐受性增强，也可诱导PNALD。结论pNALD细胞模型中诱导了IRE1α，抑制了该细胞的脂肪变性，抑制了α的α表达，减轻了脂肪变性程度。综上所述，我们的数据提示IRE1α通路可能参与了PNALD的发生发展。
AimsTo model the parenteral nutrition‐associated liver disease (PNALD) in rat normal hepatocytes BRL and investigate the role of endoplasmic reticulum stress‐ (ERS‐) related IRE1αsignal in the process of PNALD.MethodsThe BRL cells were treated with different concentrations of soybean oil emulsion (SO) to induce hepatocyte fatty degeneration. The PNALD cell disease model was further confirmed by analysis of Oil Red O staining and biochemical parameters. Next, the IRE1αwas silenced by specific shRNAs via lentivirus and the role of IRE1αin anticytotoxicity and the expression level of ERS‐related protein IRE1αand p‐IRE1αwere measured.ResultsThe results of Oil Red O staining indicated that the PNALD was successfully established in BRL cells and the CCK‐8 data indicated which 0.6% that SO was further applied to the experiment owing to its better induction of PNALD and less toxicity to the cells. Besides, the value of biochemical parameters (TBIL, DBIL, ALT, and AST) was also elevated in the SO group compared with the NG group. After knockdown of IRE1α, the PNALD was also induced while the cells were more tolerant to SO. The less positive Oil Red O staining and reduced values of biochemical parameters were observed in the shIRE1αgroup when compared to the shControl, both of which accepted SO treatment.ConclusionIRE1αwas induced in PNALD cell model and suppression of IRE1αresulted in reduced steatosis in this cell disease model. Taken together, our data suggested that the IRE1αpathway may be involved in the development of PNALD.