高剂量糖皮质激素对大鼠糖代谢的影响

doi:10.16138/j.1673-6087.2021.06.006

摘要/Abstract

摘要：

目的：探讨高剂量糖皮质激素（glucocorticoid,GC）对大鼠葡萄糖糖代谢的影响。方法：采用不同剂量（0~10 mg/kg）的地塞米松干预,选择合适的给药剂量。给予Wistar大鼠高剂量（10 mg/kg）地塞米松,观察高剂量GC对大鼠体重、空腹血糖、空腹胰岛素、糖耐量试验、胰岛素抵抗试验的影响。采用¹⁸F-氟代脱氧葡萄糖（fluorodeoxyglucose,FDG）正电子发射体层成像（positron emission tomography,PET）/CT显像,观察高剂量GC对大鼠骨骼肌、肝脏葡萄糖代谢的影响。结果：不同剂量的地塞米松均会引起糖代谢改变,其中10 mg/kg 给药剂量适用于该研究。10 mg/kg地塞米松干预后,大鼠体重明显降低[第0、3、7、11、15 天为（261±8）（226±8）（192±10）（172±10）（156±10） g,均P<0.000 1],空腹血糖[第0、3、7、11、15 天为（4.3±0.8）（14.4±5.2）（8.3±2.6）（9.8±4.4）（9.8±4.9） mmol/L,均P<0.05]和空腹胰岛素水平[第0、3、7、11、15天为（0.8±0.2）（11.6±1.1）（9.2±1.0）（9.2±2.4）（13.5±2.1） μg/L,均P<0.05]升高,血糖曲线下面积增加（第0、3、7、11、15天为858±26、2 350±345、1 680±331、1 352±166、1 553±217,均P<0.05）,胰岛素敏感性降低（第0、3、7、11、15 天为1.26±0.18、0.51±0.09、0.91±0.18、0.77±0.16、0.50±0.16,均P<0.05）。骨骼肌FDG摄取增加（第0、3、7、11、15 天为0.10±0.01、0.15±0.03、0.20±0.02、0.28±0.02、0.27±0.03,均P<0.05）,肝脏FDG摄取增加不明显,骨骼肌和肝脏糖原含量增加。结论：高剂量GC会引起明显的高血糖及高胰岛素血症。高胰岛素血症补偿了GC引起的骨骼肌胰岛素抵抗,不能完全补偿肝脏葡萄糖代谢缺陷。

关键词: 糖皮质激素, 葡萄糖代谢, 胰岛素抵抗, 正电子发射体层成像/CT

Abstract:

Objective To explore the effect of high-dose glucocorticoid(GC) on glucose metabolism in rats. Methods Choose appropriate dose in dexamethasone treatment through using different doses. By administering high-dose dexamethasone to Wistar rats, the effects of high-dose GC on rat body weight, fasting blood glucose, fasting insulin, glucose tolerance test, and insulin resistance test were observed. ¹⁸F-fluorodeoxyglucose(FDG) positron emission tomography (PET)/CT imaging was used to detect the effect of high-dose GC on glucose metabolism in skeletal muscle and liver of rats. Results Different doses of dexamethasone can cause changes in glucose metabolism, of which a dose of 10 mg/kg was suitable for this study. After high-dose dexamethasone treatment, the body weight of rats decreased[days 0,3,7,11,15 were (261±8)(226±8)(192±10)(172±10)(156±10) g, all P<0.000 1], fasting blood glucose [days 0,3,7,11,15 were(4.3±0.8)(14.4±5.2)(8.3±2.6)(9.8±4.4)(9.8±4.9) mmol/L, all P<0.05] and insulin levels increased[days 0,3,7,11,15 were (0.8±0.2)(11.6±1.1)(9.2±1.0)(9.2±2.4)(13.5±2.1) μg/L, all P<0.05], the area under the curve of glucose increased(days 0,3,7,11,15 were 858±26,2 350±345,1 680±331,1 352±166,1 553±217, all P<0.05), and insulin sensitivity decreased(days 0,3,7,11,15 were 1.26±0.18,0.51±0.09,0.91±0.18,0.77±0.16,0.50±0.16, all P<0.05). FDG uptake in skeletal muscle increased (days 0,3,7,11,15 were 0.10±0.01,0.15±0.03,0.20±0.02,0.28±0.02,0.27±0.03, all P<0.05), FDG uptake in liver didn’t change significantly, glycogen content in skeletal muscle and liver increased. Conclusions High-dose GC could cause significant hyperglycemia and hyperinsulinemia. Hyperinsulinemia compensated the insulin resistance of skeletal muscle caused by GC, however it could not completely compensate the deficiency of glucose metabolism in the liver.

Key words: Glucocorticoid, Glucose metabolism, Insulin resistance, Positron emission tomography/CT

中图分类号:

R587

赵晴晴, 周金鑫, 潘昱, 琚卉君, 朱丽颖, 刘瑒, 张一帆. 高剂量糖皮质激素对大鼠糖代谢的影响[J]. 内科理论与实践, 2021, 16(06): 397-403.

ZHAO Qingqing, ZHOU Jinxin, PAN Yu, JU Huijun, ZHU Liying, LIU Yang, ZHANG Yifan. Effect of high-dose glucocorticoid on glucose metabolism in rats[J]. Journal of Internal Medicine Concepts & Practice, 2021, 16(06): 397-403.

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