Global organ shortage has led to the acceptance of steatotic livers for transplantation, taking the risk of graft dysfunction associated with the higher sensitivity of steatotic livers to ischemia and reperfusion injury (IRI). Data about circular RNAs (circRNAs) in steatotic livers following IRI are practically nonexistent. In our study, a high‐fat diet‐fed mouse model of hepatic steatosis was generated, and RNA sequencing was performed both on IRI and on sham liver tissues of these mice to screen for circRNAs with significant differential expression. To further validate our bioinformatics data, one upregulated circRNA and four downregulated circRNAs were examined. The circularity of these circRNAs was demonstrated using RNaseR digestion and Sanger sequencing. The expression of four stable circRNAs undigested by RNaseR was further validated by quantitative PCR. In summary, this study unearths several circRNAs as novel and potentially effective targets involved in the more severe damage of steatotic livers following IRI.

中文翻译：

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新一代RNA测序对缺血再灌注损伤后脂肪变性肝脏环状RNA的综合分析

全球器官短缺导致接受脂肪肝进行移植，从而冒着与脂肪肝对缺血和再灌注损伤 (IRI) 的更高敏感性相关的移植物功能障碍的风险。关于 IRI 后脂肪变性肝脏中环状 RNA (circRNA) 的数据几乎不存在。在我们的研究中，建立了高脂肪饮食喂养的肝脂肪变性小鼠模型，并对这些小鼠的 IRI 和假肝组织进行了 RNA 测序，以筛选具有显着差异表达的 circRNA。为了进一步验证我们的生物信息学数据，检查了一个上调的 circRNA 和四个下调的 circRNA。使用 RNaseR 消化和 Sanger 测序证明了这些 circRNA 的循环性。通过定量 PCR 进一步验证了四种未被 RNaseR 消化的稳定 circRNA 的表达。总之，这项研究发现了几种 circRNAs 作为新的和潜在有效的靶点，参与 IRI 后更严重的脂肪肝损伤。