College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao 028000, China.
Key Laboratory for Prevention and Control of Herbivorous Livestock Perinatal Diseases, Inner Mongolia Minzu University, Tongliao 028000, China.
J Vet Sci. 2022 Sep;23(5):e76. doi: 10.4142/jvs.22112.
Clinical dexamethasone (DEX) treatment or stress in bovines results in extensive physiological changes with prominent hyperglycemia and neutrophils dysfunction.
To elucidate the effects of DEX treatment in vivo on cellular energy status and the underlying mechanism in circulating neutrophils.
We selected eight-month-old male bovines and injected DEX for 3 consecutive days (1 time/d). The levels of glucose, total protein (TP), total cholesterol (TC), and the proinflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in blood were examined, and we then detected glycogen and adenosine triphosphate (ATP) content, phosphofructosekinase-1 (PFK1) and glucose-6-phosphate dehydrogenase (G6PDH) activity, glucose transporter (GLUT)1, GLUT4, sodium/glucose cotransporter (SGLT)1 and citrate synthase (CS) protein expression and autophagy levels in circulating neutrophils.
DEX injection markedly increased blood glucose, TP and TC levels, the Ca/P ratio and the neutrophil/lymphocyte ratio and significantly decreased blood IL-1β, IL-6 and TNF-α levels. Particularly in neutrophils, DEX injection inhibited p65-NFκB activation and elevated glycogen and ATP contents and SGLT1, GLUT1 and GR expression while inhibiting PFK1 activity, enhancing G6PDH activity and CS expression and lowering cell autophagy levels.
DEX induced neutrophils glucose uptake by enhancing SGLT1 and GLUT1 expression and the transformation of energy metabolism from glycolysis to pentose phosphate pathway (PPP)-tricarboxylic acid (TCA) cycle. This finding gives us a new perspective on deeper understanding of clinical anti-inflammatory effects of DEX on bovine.
临床使用地塞米松（DEX）治疗或应激会导致牛产生广泛的生理变化，表现为明显的高血糖和中性粒细胞功能障碍。
阐明体内 DEX 治疗对循环中性粒细胞细胞能量状态的影响及其潜在机制。
我们选择 8 月龄雄性奶牛，连续 3 天（每天 1 次）注射 DEX。检测血液中葡萄糖、总蛋白（TP）、总胆固醇（TC）、促炎细胞因子白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子（TNF）-α水平，并检测糖原和三磷酸腺苷（ATP）含量、磷酸果糖激酶-1（PFK1）和葡萄糖-6-磷酸脱氢酶（G6PDH）活性、葡萄糖转运蛋白（GLUT）1、GLUT4、钠/葡萄糖协同转运蛋白（SGLT）1和柠檬酸合酶（CS）蛋白表达及自噬水平。
DEX 注射显著增加了血糖、TP 和 TC 水平、钙/磷比值和中性粒细胞/淋巴细胞比值，显著降低了血液中 IL-1β、IL-6 和 TNF-α水平。特别是在中性粒细胞中，DEX 注射抑制了 p65-NFκB 激活，增加了糖原和 ATP 含量，以及 SGLT1、GLUT1 和 GR 表达，同时抑制了 PFK1 活性，增强了 G6PDH 活性和 CS 表达，降低了细胞自噬水平。
DEX 通过增强 SGLT1 和 GLUT1 表达以及将能量代谢从糖酵解转化为磷酸戊糖途径（PPP）-三羧酸（TCA）循环，诱导中性粒细胞摄取葡萄糖。这一发现为我们深入理解 DEX 对牛的临床抗炎作用提供了新的视角。
