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Mass Spectrometry-Based Label-Free Quantitative Proteomic Analysis of CCl4-Induced Acute Liver Injury in Mice Intervened by Total Glycosides from Ligustri Lucidi Fructus
Current Proteomics ( IF 0.8 ) Pub Date : 2021-05-31 , DOI: 10.2174/1570164617999200728192812
Qian Lu 1 , Hai-Zhu Xing 1 , Nian-Yun Yang 1
Affiliation  

Background: CCl4 Acute Liver Injury (ALI) is a classical model for experimental research. However, there are few reports involved in the fundamental research of CCl4-induced ALI. Ligustri Lucidi Fructus (LLF) and its prescription have been used to treat hepatitis illness clinically. LLF and its active ingredients displayed anti-hepatitis effects, but the mechanism of . function has not yet been fully clarified.

Objective: To investigate the proteomic analysis of CCl4-induced ALI, and examine the effects of active Total Glycosides (TG) from LLF on ALI of mice4, including histopathological survey and proteomic changes of liver tissues, and delineate the possible underlying mechanism.

Methods: CCl4 was used to produce the ALI mice model. The model mice were intragastrically administrated with TG and the liver histopathological changes of mice were examined. At the end of the test, mice liver samples were collected, and after protein denaturation, reduction, desalination and enzymatic hydrolysis, identification was carried out by nano LC-ESI-OrbiTrap MS/MS technology. The data was processed by Maxquant software. The differentially-expressed proteins were screened and identified, and their biological information was also analyzed based on GO and KEGG analysis. Key protein expression was validated by Western blot analysis.

Results: A total of 705 differentially-expressed proteins were identified in the normal, model and administration groups. 9 significant differential proteins were focused based on the analysis. Liver protein expression changes of CCl4-induced ALI mice were mainly involved in several important signaling channels, namely FoxO signaling pathway, autophagy-animal, insulin signaling pathway. TG has an anti-liver damnification effect in ALI mice, the mechanism of which is related to FoxO1 and autophagy pathways.

Conclusion: CCl4 inhibited expression of insulin-Like growth factor 1 (Igf1) and 3-phosphoinositide- dependent protein kinase 1 (Pdpk1) in liver cells and induced insulin resistance, thus interfering with mitochondrial autophagy and regeneration of liver cells and the metabolism of glucose and lipid, and causing hepatic necrosis in mice. TG resisted liver injury in mice. TG adjusted the expression level of key proteins Igf1 and Pdpk1 after liver injury and improved insulin resistance, thus promoting autophagy and resistance to liver damage.



中文翻译:

基于质谱的无标记定量蛋白质组学分析 CCl4 诱导的小鼠急性肝损伤受女贞总糖苷干预

背景:四氯化碳急性肝损伤 (ALI) 是实验研究的经典模型。然而,关于CCl4诱导的ALI基础研究的报道很少。女贞子(LLF)及其方剂已在临床上用于治疗肝炎疾病。LLF及其活性成分显示出抗肝炎作用,但其机制。功能尚未完全阐明。

目的:研究CCl 4诱导的ALI的蛋白质组学分析,并检查LLF中活性总糖苷(TG)对小鼠ALI的影响4,包括组织病理学调查和肝组织蛋白质组学变化,并描绘可能的潜在机制。

方法:四氯化碳4被用来产生ALI小鼠模型。模型小鼠灌胃TG,观察小鼠肝脏组织病理学变化。试验结束时采集小鼠肝脏标本,经蛋白质变性、还原、脱盐、酶解后,采用纳米LC-ESI-OrbiTrap MS/MS技术进行鉴定。数据由 Maxquant 软件处理。对差异表达的蛋白质进行筛选和鉴定,并基于GO和KEGG分析对其生物学信息进行分析。通过蛋白质印迹分析验证关键蛋白表达。

结果:正常组、模型组和给药组共鉴定出705个差异表达蛋白。基于分析集中了9个显着差异蛋白。CCl 4诱导的ALI小鼠肝蛋白表达变化主要参与几个重要的信号通路,即FoxO信号通路、自噬-动物、胰岛素信号通路。TG在ALI小鼠中具有抗肝损伤作用,其机制与FoxO1和自噬通路有关。

结论:CCl 4抑制肝细胞中胰岛素样生长因子1(Igf1)和3-磷酸肌醇依赖性蛋白激酶1(Pdpk1)的表达,诱导胰岛素抵抗,从而干扰线粒体自噬和肝细胞再生及肝细胞的代谢。葡萄糖和脂质,并导致小鼠肝坏死。TG抵抗小鼠肝损伤。TG调节肝损伤后关键蛋白Igf1和Pdpk1的表达水平,改善胰岛素抵抗,从而促进自噬和肝损伤抵抗。

更新日期:2021-05-31
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