糖皮质激素诱发小鼠药源性证候模型规范化研究及其评价标准  

Standardization study and evaluation criteria of glucocorticoid-induced syndrome model in mice

作　　者：潘志强[1] 钱宏梁 李亚 王晓敏[1] 梁龙龙[1] 谢海纳 方肇勤[1] PAN Zhiqiang;QIAN Hongliang;LI Ya;WANG Xiaomin;LIANG Longlong;XIE Haina;FANG Zhaoqin(School of Basic Medical Sciences,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学基础医学院,上海201203

出　　处：《上海中医药大学学报》2021年第1期20-24,共5页Academic Journal of Shanghai University of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(81873212);上海市科委实验动物专项基金项目(19140905000).

摘　　要：目的:对糖皮质激素诱发的小鼠药源性证候模型建立规范化的造模方法及评价标准。方法:对模型动物、糖皮质激素类药物及其干预的剂量、时间等进行考察,采用小鼠辨证论治实验方法学以及反映肾上腺皮质功能的实验指标综合评价小鼠证候属性。结果:对糖皮质激素诱发的小鼠药源性证候模型,建议首选ICR小鼠,常规造模采用3.3 g·kg-1·d-1氢化可的松连续灌胃14 d;大剂量短期造模采用25 g·kg-1·d-1氢化可的松连续灌胃5 d;小剂量长期造模采用0.33 g·kg-1·d-1氢化可的松连续灌胃28 d;小剂量减停干预造模采用0.66 g·kg-1·d-1氢化可的松连续灌胃给药28 d、再剂量减半7 d、停药14 d。较理想的评价指标包括:体质量、脾脏指数、胸腺指数、腋温、体表红外温度、自主行为活跃度、四肢抓力、血液皮质酮、肾上腺类固醇激素合成酶特异性分子(StAR、CYP11A1、CYP11B1、CYP21A1、SRBI、LDLR)、肾上腺皮质形态及超微结构。结论:对糖皮质激素诱发的小鼠药源性证候模型建立了规范化的造模方法及可量化的疗效评价标准,为中药及其复方的药效研究提供理想的小鼠证候模型。Objective: To establish the standardized modeling methods and evaluation criteria for glucocorticoid-induced syndrome in mice. Methods: The model animals, glucocorticoids as well as the dosage and time of drug intervention were investigated, the experimental methodology of syndrome differentiation and treatment and the experimental indexes reflecting adrenal cortex function were used to comprehensively evaluate the syndrome attributes of mice. Results: In the study of glucocorticoid-induced syndrome model, ICR mice were suggested to be the first choice. The conventional model was established by hydrocortisone at dose of 3.3 g·kg-1·d-1 for 14 days. The short-term model with high-dose was established by hydrocortisone at dose of 25 g·kg-1·d-1 for 5 days. The long-term model with low-dose was established by hydrocortisone at dose of 0.33 g·kg-1·d-1 for 28 days. The reduction and discontinuation model with low-dose was established by 0.66 g·kg-1·d-1 hydrocortisone for 28 days, half dose for 7 days and drug withdrawal for 14 days. The ideal evaluation indexes included body mass, spleen index, thymus index, axillary temperature, body surface infrared temperature, autonomic behavior activity, limb grasp, blood corticosterone, adrenal steroid hormone synthase specific molecules(StAR, CYP11 A1, CYP11 B1, CYP21 A1, SRBI, LDLR), and morphology and ultrastructure of adrenal cortex. Conclusion: The standardized modeling methods and quantifiable evaluation standard of therapeutic effect are established for glucocorticoid-induced syndrome model in mice, which provides an ideal syndrome model for the study of pharmacodynamics of traditional Chinese medicine and compound recipes.

关 键 词：糖皮质激素 证候模型 肾上腺 氢化可的松 小鼠 

分 类 号：R-332[医药卫生]