炎症性疾病中糖皮质激素抵抗机制的研究进展.PDFVIP

Drug Evaluation Research 第40 卷 第12 期 2017 年12 月 • 1811 • 炎症性疾病中糖皮质激素抵抗机制的研究进展 1,2 2 1* 张书印 ，丁选胜 ，方 芸 1. 南京大学附属鼓楼医院，江苏 南京 210008 2. 中国药科大学，江苏 南京 211198 摘 要：糖皮质激素因其强效的抗炎作用在临床上广泛使用，但是使用中发现在严重哮喘、慢性阻塞性肺病、急性淋巴细胞 白血病、间质性肺病等炎症性疾病中有部分患者存在激素抵抗，限制了糖皮质激素的使用及预后。激素治疗患者存在糖皮质 激素激素抵抗主要是由于糖皮质激素受体蛋白表达差异、基因多态性和基因突变、细胞转录因子的异常等引起的。不同疾病 存在的糖皮质激素抵抗的机制也存在差异，对于哮喘和间质性肺病患者糖皮质激素抵抗主要是由于糖皮质受体基因多态性， 急性淋巴细胞白血病患者主要是受体蛋白的表达差异，而糖皮质激素对于慢性阻塞性肺病患者可能无效。 关键词：糖皮质激素；糖皮质激素抵抗；炎症性疾病；哮喘；慢性阻塞性肺病；间质性肺病；急性淋巴细胞白血病 中图分类号：R965 文献标志码：A 文章编号：1674-6376 (2017) 12-1811-05 DOI: 10.7501/j.issn.1674-6376.2017.12.028 Research advance on resistance mechanism of glucocorticoid in inflammtory diseases 1,2 2 1 ZHANG Shu-yin , DING Xuan-sheng , FANG Yun 1. Nanjing Drum Tower Hospital, Nanjing 210008, China 2. China Pharmaceutical University, Nanjing 211198, China Abstract: Glucocorticoid is used widely for its potent anti-inflammatory effects in clinic, however, it is found that some patients emerged resistant of hormone in some diseases such as severe asthma, chronic obstructive pulmonary, acute lymphoblastic leukemia, and interstitial lung disease, et al. This phenomenon restrict the use and prognosis of glucocorticoid. The existance of hormone resistance in patients with these diseases primarily because of glucocorticoid receptors diverse expression, gene polymorphisms, gene mutations, and abnormity of transcription factors. The mechanisms of glucocorticoid resistance are different in those diseases. In patients with asthma and interstitial lung disease, glucocorticoid resistance is mainly due to the polymorphism of the glucocorticoid receptor gene. Glucocorticoid resistance in the patients with acute lymphoblastic leukemia is primarily due to the expression differen