不同药物诱导小鼠胸腺萎缩模型的对比研究  

Comparative study of thymus atrophy models induced by different drugs in mice

作　　者：业康 栾会玲 李振皓 李振宇 孙嫣[4] 王志安[1] 金祖汉[1] 黄晶晶[1] 金捷[1] 毛培江[1] YE Kang;LUAN Hui-Ling;LI Zhen-Hao;LI Zhen-Yu;SUN Yan;WANG Zhi-An;JIN Zu-Han;HUANG Jing-Jing;JIN Jie;MAO Pei-Jiang(Zhejiang Research Institute of Chinese Medicine Co.Ltd,Hangzhou 310023,China)

机构地区：[1]浙江省中药研究所有限公司,杭州310023 [2]浙江寿仙谷植物药研究院有限公司,杭州311121 [3]金华寿仙谷药业有限公司,金华321200 [4]杭州市第一人民医院,杭州310006

出　　处：《中国免疫学杂志》2021年第7期786-790,共5页Chinese Journal of Immunology

基　　金：浙江省中医药科技计划项目(2020ZA085);浙江省食品药品检验研究院新型冠状病毒感染应急科研攻关专项(zsyjk2020001);桐乡市新型冠状病毒感染肺炎应急防治科技计划项目(202001003)。

摘　　要：目的:对比研究地塞米松、氢化可的松、聚肌胞苷酸以及苯甲酸雌二醇分别诱导的小鼠胸腺萎缩模型。方法:将55只雌性ICR小鼠分为5组,除对照组外分别给予地塞米松磷酸钠、氢化可的松、聚肌胞苷酸与苯甲酸雌二醇建立模型。观察其胸腺指数、脾脏指数、血细胞变化、血浆中MDA与GST水平、胸腺病理学检测、胸腺细胞凋亡以及相关蛋白的表达情况。结果:各模型组小鼠胸腺指数较对照组均显著降低(P<0.01)。血细胞分析结果中聚肌胞苷酸组白细胞计数低于对照组(P<0.01),雌二醇组高于对照组(P<0.05);雌二醇组淋巴细胞百分率较对照组降低(P<0.01)。地塞米松组、氢化可的松组血浆中MDA含量较对照组显著性降低,雌二醇组较对照组显著性升高(P<0.01)。胸腺HE病理学染色结果表明地塞米松与氢化可的松诱导的胸腺皮质细胞大量坏死,组织萎缩严重,而聚肌胞苷酸与苯甲酸雌二醇所诱导的模型则较轻。胸腺TUNEL检测结果发现对照组小鼠胸腺仅存在极少数细胞出现凋亡,其余组别胸腺皮质均出现大量的细胞凋亡,其中雌二醇组皮质髓质均出现较为明显的凋亡。蛋白电泳结果中地塞米松组与氢化可的松组小鼠胸腺中所测凋亡及炎症蛋白的表达量均显著低于对照组;聚肌胞苷酸组caspase-3、NF-κB激活水平与对照组无显著性差异,但其caspase-3、NF-κB蛋白的表达总量均高于对照组(P<0.05);雌二醇组NF-κB蛋白磷酸化水平以及TNF-α蛋白的表达低于对照组(P<0.05),而IL-6的表达量高于对照组(P<0.05)。结论:4种药物均能够成功诱导胸腺的萎缩,但胸腺萎缩程度存在较大差异,故药效评价时应注意模型的选择。Objective:To compare the differences in thymic atrophy mouse models respectively induced by dexamethasone,hydrocortisone,polyinosinic acid and estradiol benzoate.Methods:Fifty-five female ICR mice were divided into five groups.In addition to the control group,dexamethasone sodium phosphate,hydrocortisone,polyinosinic acid and estradiol benzoate were administered to establish models.Observe the thymus index,spleen index,blood cell changes,MDA and GST levels in plasma,thymus pathological examination,thymus cells apoptosis and expression of inflammation-related proteins.Results:The thymus index of mice in each model group was significantly reduced compared with the control group(P<0.01).In the blood cell analysis,the white blood cell count of the polyinosinc group was lower than the control group(P<0.01),and the estradiol group was higher than the control group(P<0.05).The percentage of lymphocytes in the estradiol group was lower than that in the control group(P<0.01).Plasma MDA content in dexamethasone group and hydrocortisone group was significantly lower than the control group,and estradiol group was higher than the control group(P<0.01).The pathological results showed that thymic cortex cells induced by dexamethasone and hydrocortisone had massive necrosis and severe tissue atrophy,while the model induced by the polyinosinc group and estradiol was lighter.The results of thymus apoptosis showed that only a few cells of the thymus of the control group had apoptosis,and the other groups had a large number of apoptosis,especially the estradiol group.The results of protein electrophoresis in the dexamethasone and hydrocortisone group showed significantly lower apoptosis and inflammatory protein expression in the thymus than the control group;The activation ratios of caspase-3 and NF-κB in the polyinosinc group were not significantly different from those in the control group,but the total protein expression was higher than that in the control group(P<0.05);The proportion of NF-κB phosphorylation and the expression

关 键 词：胸腺萎缩 模型 地塞米松 氢化可的松 聚肌胞苷酸 雌二醇 

分 类 号：R392.1[医药卫生—免疫学]