HSP90抑制剂17-AAG对MRL/lpr狼疮鼠的治疗作用  

Efficacy of HSP90 inhibitor 17-AAG on MRL/lpr lupus mice

作　　者：洪梁健 陈爱军[1] 李凤增[1] 方圣[1] HONG Liang-jian;CHEN Ai-jun;LI Feng-zeng;FANG Sheng(Department of Dermatology,the First Affiliated Hospital of Chongqing Medical University,CHONGQING 400016,China)

机构地区：[1]重庆医科大学附属第一医院皮肤科,重庆400016

出　　处：《中国新药与临床杂志》2020年第5期298-302,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家自然科学基金青年项目(81602752);重庆市基础与前沿研究计划一般项目(cstc2015jcyjA10082)。

摘　　要：目的观察HSP90抑制剂17-AAG对MRL/lpr狼疮小鼠的作用。方法将7周龄MRL/lpr小鼠20只,随机分为对照组和实验组。实验组经腹腔注射17-AAG 50 mg·kg-1,每周3次,连续注射7周,对照组腹腔注射等量生理盐水。每周测量小鼠体重,BCA法检测尿蛋白,每2周ELISA法检测自身抗体抗核抗体(ANA)和抗双链DNA(dsDNA)抗体。小鼠处死后观察肾脏组织病理学改变及免疫复合物沉积情况,Western blot法检测外周血单个核细胞中HSP90蛋白表达。结果对照组和实验组体重、尿蛋白浓度、ANA和抗dsDNA抗体随周龄呈上升趋势,2组间比较无显著差异(P> 0.05);从11周龄起,实验组尿蛋白、ANA和抗dsDNA抗体均显著低于对照组(P=0.047)。与对照组相比,实验组HSP90表达显著降低(P <0.05)。结论 17-AAG可使MRL/lpr狼疮鼠的尿蛋白水平降低,自身抗体产生下降,缓解症状。AIM To investigate the effect of HSP90 inhibitor 17-AAG on MRL/lpr lupus mice. METHODS Twenty 7-week-old MRL/lpr mice were randomly divided into control group and experimental group. 17-AAG 50 mg·kg-1 was intraperitoneally injected into MRL/lpr mice three times a week for 7 weeks in the experimental group, and the control group were intraperitoneally injected with the same amount of normal saline. Mouse weight was recorded and the urine protein was measured by BCA method every week. Antinuclear antibody(ANA) and anti-dsDNA antibody were detected by ELISA method every two weeks. Renal tissue biopsy was performed to observe pathological changes and immune complex deposition. Western blot was used to detect HSP90 protein expression in peripheral blood monouclear cells. RESULTS The mouse weight, urine protein concentration, ANA and anti-ds DNA antibody of the control group and the experimental group increased with the age of the week, but there was no significant difference between the two groups(P > 0.05). From the age of 11 weeks, the urine protein, ANA and anti-ds DNA antibody of the experimental group were significantly lower than those of the control group(P = 0.047). Compared with the control group, the expression of HSP90 in the experimental group decreased significantly(P < 0.05). CONCLUSION 17-AAG can reduce urine protein levels and the autoantibody production, and alleviate the symptoms in MRL/lpr lupus mice.

关 键 词：红斑狼疮 系统性 17-AAG HSP90热休克蛋白质类 

分 类 号：R986[医药卫生—药品]