He Wei, Pan Huafeng, Tao Ping, Lin Jiang, Zhang Beiping, Wang Shiying
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Ann Transl Med. 2022 Feb;10(4):218. doi: 10.21037/atm-22-566.
Colonic mucosal injuries are an important manifestation of ulcerative colitis (UC), which is related to hypoxia-induced glycolysis in colonic mucosal epithelial cells (cmECs). Panax notoginseng (PN) promotes the repair of colonic mucosal injuries by inhibiting hypoxia-induced glycolysis in cmECs; However, the mechanism by which this occurs is not completely clear. Here, we are to investigate the effects of PN on glucose metabolism in cmECs in colitis and the underlying mechanism.
A model of dextran sulfate sodium-induced colitis rats was used in this research, and the severity of colitis was assessed by pathology, disease activity index (DAI), and weight changes. The content of intracellular pyruvate, intracellular lactate, adenosine triphosphate (ATP), reactive oxygen species (ROS), mitochondrial ROS (mtROS), myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, and inflammatory cytokines was detected by assay kits. The expression levels of proteins were detected by western blotting. The expression levels of the ATP4a gene were detected by quantitative polymerase chain reaction (QT-PCR).
The colonic mucosal injuries of the colitis rats were significantly worse than those of the control group. Specifically, the hypoxia-induced glycolysis and potential of hydrogen (pH) in the colonic lumen were increased, and the expression of ATP4a was downregulated in the colitis rats. PN (1.0 g/kg) promoted the repair of colonic mucosal injuries, and reversed the pH in the colonic lumen. Further, PN increased the expression of ATP4a proteins, the content of ATP, and the SOD activity, and decreased the expression of pyruvate dehydrogenase lipoamide kinase isozyme and hypoxia-inducible factor 1-alpha proteins, the content of ROS, and MPO activity in cmECs in colitis. PN also increased the expression of ATP4a, cytochrome P450 family 21 subfamily a member 2, and hydroxy-delta-5-steroid dehydrogenase, 3 beta and steroid delta-isomerase 2 proteins in the mitochondria, and decreased the content of mtROS in cmECs.
PN alleviated the pH in the colonic lumen and hypoxia-induced glycolysis in cmECs by reducing the hypoxia-induced glycolysis caused by the downregulation of ATP4a protein, thereby promoting the repair of colonic mucosal injuries in colitis.
结肠黏膜损伤是溃疡性结肠炎（UC）的重要表现，这与结肠黏膜上皮细胞（cmECs）中缺氧诱导的糖酵解有关。三七（PN）通过抑制cmECs中缺氧诱导的糖酵解来促进结肠黏膜损伤的修复；然而，其发生机制尚不完全清楚。在此，我们旨在研究PN对结肠炎中cmECs葡萄糖代谢的影响及其潜在机制。
本研究采用葡聚糖硫酸钠诱导的结肠炎大鼠模型，并通过病理学、疾病活动指数（DAI）和体重变化评估结肠炎的严重程度。使用检测试剂盒检测细胞内丙酮酸、细胞内乳酸、三磷酸腺苷（ATP）、活性氧（ROS）、线粒体ROS（mtROS）、髓过氧化物酶（MPO）活性、超氧化物歧化酶（SOD）活性和炎性细胞因子的含量。通过蛋白质印迹法检测蛋白质的表达水平。通过定量聚合酶链反应（QT-PCR）检测ATP4a基因的表达水平。
结肠炎大鼠的结肠黏膜损伤明显比对照组严重。具体而言，结肠炎大鼠结肠腔内缺氧诱导的糖酵解和氢离子（pH）电位升高，且ATP4a的表达下调。PN（1.0 g/kg）促进了结肠黏膜损伤的修复，并逆转了结肠腔内的pH值。此外，PN增加了ATP4a蛋白的表达、ATP的含量和SOD活性，并降低了结肠炎cmECs中丙酮酸脱氢酶硫辛酰胺激酶同工酶和缺氧诱导因子1-α蛋白的表达、ROS的含量以及MPO活性。PN还增加了线粒体中ATP4a、细胞色素P450家族21亚家族a成员2和羟基-δ-5-类固醇脱氢酶、3β和类固醇δ-异构酶2蛋白的表达，并降低了cmECs中mtROS的含量。
PN通过减少ATP4a蛋白下调引起的缺氧诱导糖酵解，减轻了结肠腔内的pH值和cmECs中缺氧诱导的糖酵解，从而促进了结肠炎中结肠黏膜损伤的修复。
