Proteomic analysis of Biliverdin protected cerebral ischemia-reperfusion injury in rats.
Proteomic analysis of Biliverdin protected cerebral ischemia-reperfusion injury in rats.
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DOI：
10.1038/s41598-023-47119-3
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发表时间：
2023-11-22
影响因子：
4.6
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中科院分区：
文献类型：
--
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胆绿素是一种血红素代谢物，有研究表明它可以减轻脑缺血再灌注损伤（CIRI）。然而，这种治疗背后的脑蛋白质组谱的改变仍然难以捉摸。本研究的目的是分析胆绿素抗CIRI大鼠大脑皮层差异蛋白表达谱，为寻找特异性标志蛋白提供实验基础。建立MCAO/R大鼠模型，通过HE染色、TTC染色、TUNEL染色、神经行为学检查、转角实验、粘连清除实验验证胆绿素的作用，结果表明胆绿素对CIRI有明显的缓解作用。此外，使用基于TMT的定量蛋白质组学方法结合LC-MS/MS技术对胆绿素治疗后接受CIRI的大鼠脑组织进行蛋白质组学分析，以阐明胆绿素在CIRI中的综合机制。首先，我们对TMT实验进行了严格的质量控制数据。最后，共鉴定了7366种蛋白质，其中95种蛋白质在CIRI组和Sham组之间差异表达（DEPs），52种在CIRI组和BV组之间差异表达（DEPs）。此外，通过RT-qPCR和Western blotting验证了147个DEP中的两个重叠蛋白Atg 4c和Camlg，其水平与TMT分析结果一致。综上所述，目前的研究结果首次绘制了胆绿素治疗CIRI后的全面蛋白质组变化，为开发胆绿素抗CIRI的潜在治疗靶点和中风的临床预后生物标志物提供了基础。
Biliverdin, a heme metabolite, has been previously reported to alleviate cerebral ischemic reperfusion injury (CIRI). However, the alterations of brain proteome profiles underlying this treatment remain elusive. The objective of this study is to analyze the differential protein expression profile in cerebral cortex of rats involved in anti-CIRI effects of Biliverdin, providing experimental foundation for searching specific marker proteins. Rat model of MCAO/R was established, HE staining, TTC staining, TUNEL staining, and neurological behavioral examination, corner turning test, adhesive removal test, were performed to validate the effects of Biliverdin, and the results indicated that Biliverdin plays a significant role in alleviating CIRI. Furthermore, proteomic analysis of brain tissues of rats subjected to CIRI following Biliverdin treatment was performed using an integrated TMT-based quantitative proteomic approach coupled with LC-MS/MS technology to clarify the comprehensive mechanisms of Biliverdin in CIRI. First, we conducted strict quality control data for TMT experiments. Finally, a total of 7366 proteins were identified, of which 95 proteins were differentially expressed (DEPs) between the CIRI group and the Sham group and 52 between the CIRI and BV groups. In addition, two overlapping proteins among the 147 DEPs, Atg4c and Camlg, were validated by RT-qPCR and western blotting, and their levels were consistent with the results of TMT analysis. Taken together, the current findings firstly mapped comprehensive proteomic changes after CIRI treated with Biliverdin, providing a foundation for developing potentially therapeutic targets of anti-CIRI of Biliverdin and clinically prognostic biomarkers of stroke.
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影响因子：
5.4
作者：
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