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钙调磷酸酶抑制剂诱导药物性高血糖的机制及临床研究进展
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| 篇名： | 钙调磷酸酶抑制剂诱导药物性高血糖的机制及临床研究进展 |
| TITLE： | Mechanism and clinical research progress of calcineurin inhibitor-induced hyperglycemia |
| 摘要： | 钙调磷酸酶抑制剂（CNI）属于强效免疫抑制剂，是器官移植和自身免疫性疾病治疗的核心药物，以环孢素A和他克莫司为代表。长期应用CNI可导致药物性高血糖，严重影响患者预后。其发病机制涉及多层面的病理改变：在胰岛β细胞层面，CNI可通过诱导钙超载、氧化应激和线粒体功能障碍，抑制胰岛素合成关键因子表达并促进细胞凋亡，直接造成β细胞损伤；在外周组织层面，CNI可干扰胰岛素受体底物磷酸化，抑制磷脂酰肌醇3-激酶/蛋白激酶B通路，导致葡萄糖摄取减少和胰岛素抵抗；此外，CNI还可通过抑制胰高血糖素样肽1分泌及其受体信号转导，并通过激活核因子κB通路促进炎症反应，引起β细胞损伤。临床研究显示，CNI相关高血糖的发生率与药物种类、剂量及患者个体因素密切相关。针对高危患者，推荐调整CNI剂量，必要时换用低代谢毒性药物，并根据血糖水平选择合适的降糖方案。未来需深入阐明CNI代谢毒性的分子机制，优化个体化药物治疗策略，以改善患者长期预后。 |
| ABSTRACT： | Calcineurin inhibitor（CNI） is potent immunosuppressive agents and serve as cornerstone therapies in the treatment of organ transplantation and autoimmune diseases， with cyclosporine A and tacrolimus being the representative drugs. Long-term use of CNI can lead to drug-induced hyperglycemia， severely affecting patients’ prognosis. The pathogenesis involves multilevel pathological alterations： at the pancreatic β-cell level， CNI directly damage β-cell by inducing calcium overload， oxidative stress， and mitochondrial dysfunction， suppressing the expression of key insulin synthesis factors and promoting apoptosis； in peripheral tissues， CNI interfere with insulin receptor substrate phosphorylation and inhibit the phosphatidylinositol 3 kinase/protein kinase B signaling pathway， resulting in decreased glucose uptake and insulin resistance； additionally， CNI can also induce β-cell injury by suppressing the secretion and receptor signal transduction of glucagon-like peptide-1， as well as by activating the nuclear factor kappa B pathway to promote inflammatory responses. Clinical studies demonstrate that the incidence of CNI-associated hyperglycemia is closely related to drug type， dosage， and individual patient factors. For high-risk patients， dose adjustment of CNI， switching to agents with lower metabolic toxicity when necessary， and selection of appropriate glucose-lowering regimens based on glycemic levels are recommended. Future research should further elucidate the molecular mechanisms of CNI metabolic toxicity and optimize individualized pharmacotherapy strategies to improve long-term patient outcomes. |
| 期刊： | 2026年第37卷第03期 |
| 作者： | 鲁素娜；闵秋霞；文茜；张玲 |
| AUTHORS： | LU Suna，MIN Qiuxia，WEN Xi，ZHANG Ling |
| 关键字： | 药物性高血糖；钙调磷酸酶抑制剂；他克莫司；环孢素A；胰岛素抵抗；胰岛β细胞 |
| KEYWORDS： | drug-induced hyperglycemia； calcineurin inhibitor； tacrolimus； cyclosporine A； insulin resistance； pancreatic β-cell |
| 阅读数： | 11 次 |
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