摘要
目的:通过皮下注射甲状腺膜抗原,制备Graves病大鼠模型,用于候选药物的药效评价。方法:提取SD大鼠甲状腺膜蛋白,与弗氏完全佐剂以1∶1的比例乳化制备膜抗原。SD雌性大鼠分为对照组和9个致敏-发敏梯度时间间隔的造模组,造模组大鼠四肢皮下注射膜抗原,3次致敏,3次发敏。d110进行症状评分,d115进行心电图检测,ELISA检测血清总三碘甲腺原氨酸(T3)、总甲状腺素(T4)、促甲状腺激素受体抗体(TRAb)和干抗素-γ(IFN-γ),HE染色观察甲状腺和脾脏病理变化;Graph Pad Prism 5软件计算回归时效方程,确定致敏和发敏时间间隔的半数有效时间(ET50)。结果:指标效能与对数间隔时间回归所得时效曲线呈"S"型,方程为Y=0.03+0.69/[1+10(7.71 x-21.35)],ET50=587.10 h。结论:本实验通过确定膜抗原致敏与发敏的最适时间间隔,制备了Graves病药效模型,该模型符合临床表现与发病机制,可用于候选药的药效评价。
Objective:To establish a model of Graves’disease in rats by subcutaneous injection of membrane antigen for evaluating pharmacodynamics of drug candidates.Methods:The membrane protein was extracted from thyroid gland of rats and was emulsified with complete Freund’s adjuvant(CFA)by 1∶1 in volume.The SD female rats were divided into control group and 9 model groups with gradient intervals between the primary sensitization and the first challenge.The model groups were subcutaneously injected with membrane antigen to induce autoimmune injuries of thyroid(three times for sensitization and three times for challenge).The clinical symptoms were scored at d110,and ECG was detected at d115.Serum levels of T3,T4,thyrotropin receptor antibodies(TRAb)and IFN-γwere measured.The thyroid and spleen pathological changes were observed by HE staining.Graph Pad Prism 5 software was used to calculate regression validity equation to determine the half effective time(ET50)of the sensitization and sensitization interval.Results:The regressive curve was set up between the potency of indicators and the logarithm intervals.The curve presented S type with equation of Y=0.03+0.69/[1+10(7.71 x-21.35)]and ET50 of 587.10 h.Conclusion:The optimal interval between sensitization and challenge has been confirmed to set up the pharmacodynamic model of Graves’disease,which is accordance with the pathogenesis and clinical manifestations,and can be used to evaluate therapeutic effects of drug candidates.
作者
武晓玉
王宏雅
刘慧萍
丛旖君
赵欣
蔡大勇
Wu Xiaoyu;Wang Hongya;Liu Huiping;Cong Yijun;Zhao Xin;Cai Dayong(Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100193,China)
出处
《中国药师》
CAS
2021年第5期801-806,共6页
China Pharmacist
基金
国家自然科学基金青年科学基金项目(编号:81903864)
国家自然科学基金项目(编号:81673674)。
关键词
GRAVES病
大鼠
药效模型
膜抗原
Graves’disease
Rats
Pharmacodynamics model
Membrane antigen
