This study intended to investigate the role of NFKB1 in oxidative stress injury and insulin resistance in gestational hypertension (GH) mice. Following establishment of a GH mouse model by high-fat diet, NFKB1, miR-106a, and FLOT2 expression was detected in liver of mice. After NFKB1, miR-106a, and FLOT2 were altered in GH mice by lentiviral vector, oxidative stress markers in liver tissues were examined by colorimetry, and insulin resistance was assessed by fasting blood glucose and fasting insulin levels. Next, hepatocytes were isolated from GH mice and treated with miR-106a mimic, inhibitor or siRNA, followed by determination of hepatocyte apoptosis and the expression of inflammation- and apoptosis-related factors. Evaluation of the correlations among NFKB1, miR-106a, and FLOT2 were conducted. Liver of GH mice harbored NFKB1 and FLOT2 upregulation and miR-106a downregulation. miR-106a was transcriptionally inhibited by NFKB1, and negatively targeted FLOT2. Oxidative stress injury and insulin resistance in GH mice and apoptosis and inflammation of hepatocytes from GH mice were decreased after silencing NFKB1 or FLOT2 or overexpressing miR-106a. These findings provided evidence demonstrating the inhibitory effect of NFKB1 silencing on oxidative stress injury and insulin resistance in GH mice via miR-106a upregulation and FLOT2 downregulation.

本研究旨在探讨 NFKB1 在妊娠期高血压 (GH) 小鼠氧化应激损伤和胰岛素抵抗中的作用。通过高脂饮食建立GH小鼠模型后，在小鼠肝脏中检测到NFKB1、miR-106a和FLOT2的表达。通过慢病毒载体在 GH 小鼠中改变 NFKB1、miR-106a 和 FLOT2 后，通过比色法检查肝组织中的氧化应激标志物，并通过空腹血糖和空腹胰岛素水平评估胰岛素抵抗。接下来，从 GH 小鼠中分离肝细胞并用 miR-106a 模拟物、抑制剂或 siRNA 处理，然后测定肝细胞凋亡以及炎症和凋亡相关因子的表达。对 NFKB1、miR-106a 和 FLOT2 之间的相关性进行了评估。GH 小鼠的肝脏具有 NFKB1 和 FLOT2 上调和 miR-106a 下调。miR-106a 被 NFKB1 转录抑制，并负向靶向 FLOT2。在沉默 NFKB1 或 FLOT2 或过表达 miR-106a 后，GH 小鼠的氧化应激损伤和胰岛素抵抗以及来自 GH 小鼠的肝细胞的凋亡和炎症降低。这些发现提供了证据，证明 NFKB1 沉默通过 miR-106a 上调和 FLOT2 下调对 GH 小鼠的氧化应激损伤和胰岛素抵抗具有抑制作用。在沉默 NFKB1 或 FLOT2 或过表达 miR-106a 后，GH 小鼠的氧化应激损伤和胰岛素抵抗以及来自 GH 小鼠的肝细胞的凋亡和炎症降低。这些发现提供了证据，证明 NFKB1 沉默通过 miR-106a 上调和 FLOT2 下调对 GH 小鼠的氧化应激损伤和胰岛素抵抗具有抑制作用。在沉默 NFKB1 或 FLOT2 或过表达 miR-106a 后，GH 小鼠的氧化应激损伤和胰岛素抵抗以及来自 GH 小鼠的肝细胞的凋亡和炎症降低。这些发现提供了证据，证明 NFKB1 沉默通过 miR-106a 上调和 FLOT2 下调对 GH 小鼠的氧化应激损伤和胰岛素抵抗具有抑制作用。