HSP60对铅与高血压联合暴露致小鼠学习记忆功能损伤的干预作用  

Intervention effect of HSP60 on learning and memory impairment induced by combined exposure to lead and hypertension in mice

作　　者：李欣颖 朱毅 冯佩佩 王健 陈松 王伟轩 王玉君 张艳淑 LI Xinying;ZHU Yi;FENG Peipei;WANG Jian;CHEN Song;WANG Weixuan;WANG Yujun;ZHANG Yanshu(School of Public Health,North China University of Science and Technology,Tangshan,Hebei 063210,China;不详)

机构地区：[1]华北理工大学公共卫生学院,河北唐山063210 [2]华北理工大学河北省煤矿卫生与安全重点实验室,河北唐山063210 [3]华北理工大学附属医院,河北唐山063210 [4]华北理工大学实验动物中心,河北唐山063210 [5]唐山市第七医院,河北唐山063210

出　　处：《中国职业医学》2024年第2期138-143,共6页China Occupational Medicine

基　　金：国家自然科学基金(82073598);中央引导地方项目(236Z7728G)。

摘　　要：目的探讨热休克蛋白60(HSP60)对铅与高血压联合暴露致小鼠学习记忆功能损伤的作用,以及髓样细胞激发受体2(TREM2)在其中的作用机制。方法将无特定病原体级雄性C57BL/6J小鼠随机分为对照组、高血压组、铅暴露组和铅暴露+高血压组,同时另设对照组、铅暴露+高血压组和HSP60干预组,每组10只。高血压组和铅暴露+高血压组小鼠均腹腔注射剂量为0.5 mg(/kg·d)的血管紧张素Ⅱ,连续7 d,制备高血压模型。其后,铅暴露组、铅暴露+高血压组和HSP60干预组小鼠均饮用质量浓度为250 mg/L的乙酸铅饮用水,对照组、高血压组和HSP60对照组小鼠均饮用纯净水,连续12周。第12周时,HSP60对照组和HSP60干预组小鼠均予腹腔注射剂量为4 mg/kg体质量的HSP60溶液,每2天1次,共3次。采用Morris水迷宫实验检测小鼠学习记忆能力;海马组织中的白细胞介素(IL)-1β、IL-6和肿瘤坏死因子-α(TNF-α)水平以酶联免疫吸附实验检测,离子钙接头蛋白1(IBA1)和TREM2蛋白表达以蛋白质印迹法检测。结果(1)高血压组和铅暴露组小鼠穿台次数均少于对照组(P值均<0.05);与对照组、高血压组和铅暴露组比较,铅暴露+高血压组小鼠第3天的逃避潜伏期延长(P值均<0.05),穿台次数减少(P值均<0.05)。与对照组比较,其余3组小鼠海马组织中IL-1β、IL-6和TNF-α水平均升高(P值均<0.05),铅暴露组和铅暴露+高血压组小鼠海马组织中IBA1蛋白相对表达水平均升高(P值均<0.05),但TREM2蛋白相对表达水平均下降(P值均<0.05)。铅暴露+高血压组小鼠海马组织中IL-1β、IL-6、TNF-α水平和IBA1蛋白相对表达水平均高于高血压组(P值均<0.05),TREM2蛋白相对表达水平低于高血压组(P<0.05)。铅暴露+高血压组小鼠海马组织中TNF-α水平和IBA1蛋白相对表达水平均高于铅暴露组(P值均<0.05)。(2)铅暴露+高血压组小鼠逃避潜伏期长于对照组(P<0.05),穿台次数少于对照组(P<0.05)。与Objective To investigate the intervention effect of heat shock protein 60(HSP60)on learning and memory impairment induced by combined exposure to lead and hypertension in mice,and the relative mechanism of triggering receptor expressed on myeloid cells 2(TREM2).Methods Specific pathogen-free C57BL/6J male mice were randomly divided into control group,hypertension group,lead-exposed group and lead-exposed+hypertension group,or into control group,heat shock protein 60(HSP60)control group,lead-exposed+hypertension group and HSP60 intervention group,with 10 mice in each group.Mice of hypertension group and lead-exposed+hypertension group were intraperitoneally injected with angiotensinⅡat a dose of 0.5 mg(/kg·d)for seven consecutive days to induce hypertension model.Mice of the lead-exposed group,leadexposed+hypertension group,and HSP60 intervention group were given lead acetate drinking water with a mass concentration of 250.0 mg/L,while mice in the control group,hypertension group,and HSP60 control group were given purified water for 12 weeks.Mice of the HSP60 control group and HSP60 intervention group were intraperitoneally injected with a solution of HSP60 at a dose of 4 mg/kg body weight,every other day for a total of three times at the 12th week.The learning and memory ability of mice was detected using the Morris water maze test.The enzyme-linked immunosorbent assay was used to detect the levels of interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(TNF-α)in the hippocampal tissues of the mice.The relative expression of ionized calcium binding adaptor molecule-1(IBA1)and TREM2 protein in the hippocampus of mice was detected using Western blot.Results i)The number of platform crossings of the mice in the hypertension group and the lead-exposed group was lower than that in the control group(both P<0.05).The escape latency of the mice on the third day was longer and the number of platform crossings was lower in the lead-exposed+hypertension group compared with the control group,hypertension group and lead-e

关 键 词：铅 高血压 髓样细胞触发受体2 学习记忆功能 热休克蛋白60 海马组织 小鼠 

分 类 号：R135.11[医药卫生—劳动卫生]