基因敲入小鼠甲亢性低钾型周期性麻痹模型的评价  

Evaluation of the CaV1.1-R528H gene knock-in mouse model of thyrotoxic hypokalemic periodic paralysis

作　　者：智红叶 徐宏燕[1] 陈瑛瑛[2] 陈亚宁[2] 周丽君[3] 战大伟[4] 颜克松[4] 姚合斌[1,2] 

机构地区：[1]安徽医科大学海军临床学院,北京100048 [2]中国人民解放军海军总医院内分泌科,北京100048 [3]中国人民解放军海军总医院海战伤基础研究中心,北京100048 [4]中国人民解放军总医院第一附属医院实验动物科,北京100048

出　　处：《中国实验动物学报》2016年第4期369-374,共6页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金资助项目(编号:30671006;81170800);北京市自然科学基金(编号:7154240)

摘　　要：目的用基因敲入Ca V1.1-R528H小鼠建立甲亢性低钾型周期性麻痹模型并对其进行评价。方法8周龄基因敲入Ca V1.1-R528H雄性小鼠及8周龄野生型C57BL/6J雄性小鼠各36只,采用三因素两水平2×2×2析因设计方法按体重随机原则(三因素分别为突变、甲状腺素及胰岛素因素,两水平为有或无)分为8组。其中有甲状腺素处理组的小鼠制备高甲状腺素毒症,按350μg/kg体重连续腹腔注射左旋甲状腺素钠12 d,末次给药后有胰岛素处理组按0.8 U/kg体重给予腹腔注射短效胰岛素,分别检测并记录各组小鼠注射前(0 min)及注射后(30、60 min)的血钾。结果 (1)制备高甲状腺素毒症的小鼠出现烦躁不安、易激怒及毛色枯燥现象,相比对照组,饮食及饮水量明显增多,而体重增加缓慢。甲状腺功能检测显示T3、T4明显高于相应对照组,TSH明显低于相应对照组,且差异均有显著性(P<0.05)。(2)单独给予甲状腺素或胰岛素处理,突变组与野生组血钾同时间点比较并没有统计学差异,而在高甲状腺素毒症下给予胰岛素处理后,突变组与野生组同时间点(30、60 min)比较突变组血钾显著低于野生组(P<0.05)。(3)主效应及交互作用:单独突变因素或甲状腺素因素对血钾并没有作用,仅有胰岛素对降低血钾有作用(P<0.05);甲状腺素因素和突变因素之间以及胰岛素因素和突变因素之间均有交互作用(P<0.05);甲状腺素因素和胰岛素因素之间没有交互作用。结论 (1)高甲状腺素毒症制备成功。(2)利用基因敲入Ca V1.1-R528H小鼠成功的建立了甲亢性低钾型周期性麻痹模型。Objective To establish and evaluate the CaV 1. 1-R528 H gene knock-in mouse model of thyrotoxic hypokalemic periodic paralysis. Methods Thirty-six 8-week-old male CaV 1. 1-R528 H gene knock-in mice and thirty-six 8-week-old wild-type male C57 BL /6J mice were used in this study. Using three-factor two-level 2 × 2 × 2 factorial design（ the three factors including mutation,thyroxine and insulin,and two levels were with or without）,the mice were divided into 8 groups. The thyroxine groups were intraperitoneally injected with levothyroxine in a dose of 350 μg / kg once per dayfor 12 consecutive days to produce thyrotoxicosis. The insulin groups were intraperitoneally injected with short-acting insulin in a dose of 0. 8 U / kg after the last administration of levothyroxine,and the potassium levels of different groups were measured and recorded before（ 0 min） and after insulin injection（ 30 min,60 min）. Results（ 1） Compared with the control group,the following phenomena including irritability,dull coat,increased diet and water intake,and slow body weight gain,were observed in the thyrotoxic mice. Thyroid function tests showed that the levels of T3 and T4 in the thyrotoxic mice were significantly higher than those in the corresponding control mice（ P 〈 0. 05）,and the TSH level was significantly lower than that of the corresponding control mice（ P 〈 0. 05）.（ 2） After administration of insulin or thyroxine alone,the potassium levels in the mutant and wild-type mice were not significantly different. However,after combined administration of thyroxine and insulin,the potassium levels in the mutant group were significantly lower than those in the wild-type mice at30 min and 60 min（ P 〈 0. 05 for both）.（ 3） The main effects and interactions： Mutation factor or thyroxine factor alone did not influence on the potassium level,only insulin showed hypokalemic effect（ P 〈 0. 05）. There were interactions between thyroxine and mutation,and between insulin and mutation（ P 〈 0. 05

关 键 词：甲亢性低钾型周期性麻痹 基因敲入 CA V1.1-R528H小鼠 高甲状腺素毒症 胰岛素 

分 类 号：Q95-33[生物学—动物学]