Department of Medical Cell Biology, Integrative Physiology, Uppsala University, Uppsala, Sweden.
Department of Surgical Sciences, Anesthesia and Intensive Care Medicine, Uppsala University, Uppsala, Sweden.
Physiol Rep. 2021 Dec;9(23):e15142. doi: 10.14814/phy2.15142.
Acute kidney injury (AKI) is a common perioperative complication that is associated with increased mortality. This study investigates the renal gene expression in male Long-Evans rats after prolonged anesthesia and surgery to detect molecular mechanisms that could predispose the kidneys to injury upon further insults. Healthy and streptozotocin diabetic rats that underwent autoregulatory investigation in an earlier study were compared to rats that were sacrificed quickly for mRNA quantification in the same study. Prolonged surgery caused massive changes in renal mRNA expression by microarray analysis, which was validated by quantitative real-time PCR with good correlation. Furthermore, bioinformatics analysis using gene ontology and pathway analysis identified biological processes involved in immune system activation, such as immune system processes (p = 1.3 × 10 ), immune response (p = 1.3 × 10 ), and regulation of cytokine production (p = 1.7 × 10 ). PCR analysis of specific cell type markers indicated that the gene activation in kidneys was most probably macrophages, while granulocytes and T cell appeared less activated. Immunohistochemistry was used to quantify immune cell infiltration and showed no difference between groups indicating that the genetic activation depends on the activation of resident cells, or infiltration of a relatively small number of highly activated cells. In follow-up experiments, surgery was performed on healthy rats under standard and sterile condition showing similar expression of immune cell markers, which suggests that the inflammation was indeed caused by the surgical trauma rather than by bacterial infection. In conclusion, surgical trauma is associated with rapid activation of immune cells, most likely macrophages in rat kidneys.
急性肾损伤（AKI）是一种常见的围手术期并发症，与死亡率增加有关。本研究调查了雄性 Long-Evans 大鼠在长时间麻醉和手术后的肾脏基因表达，以检测可能导致肾脏在受到进一步损伤时易受损伤的分子机制。本研究中，与快速处死进行 mRNA 定量的大鼠相比，在早期研究中进行自身调节研究的健康和链脲佐菌素糖尿病大鼠被进行了比较。通过微阵列分析发现，长时间手术导致肾脏 mRNA 表达发生巨大变化，实时定量 PCR 验证具有良好相关性。此外，使用基因本体和通路分析的生物信息学分析确定了参与免疫系统激活的生物学过程，如免疫系统过程（p = 1.3×10-4）、免疫反应（p = 1.3×10-4）和细胞因子产生的调节（p = 1.7×10-4）。特定细胞类型标记物的 PCR 分析表明，肾脏中的基因激活最可能是巨噬细胞，而粒细胞和 T 细胞的激活程度较低。免疫组织化学用于定量免疫细胞浸润，结果表明各组之间无差异，表明基因激活依赖于驻留细胞的激活或相对较少的高度激活细胞的浸润。在后续实验中，在标准和无菌条件下对健康大鼠进行手术，显示出类似的免疫细胞标记物表达，这表明炎症确实是由手术创伤引起的，而不是由细菌感染引起的。总之，手术创伤与大鼠肾脏中免疫细胞的快速激活有关，最有可能是巨噬细胞。
