摘要
目的 探讨右美托咪定(Dex)对脓毒症小鼠认知功能及热休克蛋白70(HSP70)表达的影响,为其脑保护机制的研究提供参考。方法 将80只C57BL/6小鼠随机分为对照组(CON组)、单纯Dex组(Dex组)、脓毒血症组(LPS组)和Dex+脓毒血症组(D+L组),每组20只。首先,Dex组和D+L组腹腔注射Dex 25μg/kg,CON组和LPS组腹腔注射等剂量的生理盐水;30 min后LPS组和D+L组腹腔注射5 mg/kg脂多糖(LPS)复制脓毒血症模型,CON组和Dex组腹腔注射等剂量的生理盐水。采用Morris水迷宫实验评估小鼠学习记忆能力,酶联免疫吸附试验检测血清肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)水平,化学比色法检测海马组织过氧化物歧化酶(SOD)活性和谷胱甘肽(GSH)、丙二醛(MDA)水平,苏木精-伊红染色观察海马CA1区病理变化,免疫组织化学染色和实时荧光定量聚合酶链反应检测海马HSP70蛋白、mRNA表达。结果 各组小鼠第1、2、3、4、5天逃避潜伏期比较,经重复测量设计的方差分析,结果:(1)不同时间点的逃避潜伏期比较,差异有统计学意义(P <0.05);(2)各组小鼠的逃避潜伏期比较,差异有统计学意义(P <0.05),LPS组较CON组延长,D+L组较LPS组缩短;(3)各组小鼠逃避潜伏期变化趋势比较,差异有统计学意义(P <0.05)。各组小鼠游泳速度比较,差异无统计学意义(P>0.05)。LPS组目标象限停留时间短于CON组(P <0.05),D+L组长于LPS组(P <0.05);LPS组穿越平台次数少于CON组(P <0.05);D+L组多于LPS组(P <0.05)。LPS组血清TNF-α、IL-1β水平较CON组升高(P <0.05),D+L组较LPS组降低(P <0.05)。LPS组GSH、SOD水平较CON组降低(P <0.05),MDA水平较CON组升高(P <0.05),D+L组GSH、SOD水平较LPS组升高(P <0.05),MDA水平较LPS组下降(P <0.05)。LPS组HSP70蛋白阳性表达率较CON组升高(P <0.05),D+L组较LPS组升高(P <0.05),Dex组与CON组比较,差异无统计学意义(P>0.05)。LPS组HSP70 mRNA相对表达量较CON组升高(P <0.05),D+L组较LPS组升高(P
Objective To explore the effects of dexmedetomidine(Dex)on cognitive function and HSP70 expression in mice models of sepsis,and to provide a basis for researches on brain protection in the setting of sepsis.Methods Eighty C57BL/6 mice were randomly divided into control group(CON group),Dex-only group(DEX group),sepsis group(LPS group),and Dex+sepsis group(D+L group),with 20 mice in each group.Firstly,DEX group and D+L group received 25μg/kg of Dex via intraperitoneal injection,while CON group and LPS group were given the same volume of normal saline.Thirty minutes later,5 mg/kg of lipopolysaccharide(LPS)was injected intraperitoneally in LPS group and D+L group to establish models of sepsis,while CON group and DEX group were given the same volume of normal saline.The Morris water maze was performed to assess the learning and memory of mice.The serum levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were measured by ELISA,and levels of superoxide dismutase(SOD),glutathione(GSH)and malondialdehyde(MDA)in the hippocampus of mice were detected by chemical colorimetry.The hematoxylin-eosin(HE)staining was applied to observe the pathological changes in the hippocampal CA1 region,and the immunohistochemical assay and qPCR were used to determine the protein and mRNA expressions of heat shock protein 70(HSP70)in the hippocampus.Results The escape latency of mice in each group on the 1st,2nd,3rd,4th and 5th day were compared via repeated measures ANOVA,and the results revealed that the escape latency was significantly different among the time points(P<0.05)and the groups(P<0.05),and that the escape latency in the LPS group was longer than that in the CON group while that in the D+L group was shorter than that in the LPS group.Besides,the change trends of the escape latency were different among the groups(P<0.05).There was no statistically significant difference in swimming speed of mice among different groups(P>0.05).The time spent in the target quadrant in the LPS group was shorter than that in the CON
作者
赵园园
邱高林
蔡雯
周静文
李元海
夏晓琼
张梦英
Zhao Yuan-yuan;Qiu Gao-lin;Cai Wen;Zhou Jing-wen;Li Yuan-hai;Xia Xiao-qiong;Zhang Meng-ying(Department of Anesthesiology,Chaohu Hospital Affiliated to Anhui Medical University,Chaohu,Anhui 238000,China;Department of Anesthesiology,The First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230031,China)
出处
《中国现代医学杂志》
CAS
北大核心
2023年第24期29-35,共7页
China Journal of Modern Medicine
基金
国家自然科学基金(No:82101349)。
关键词
脓毒症
右美托咪定
氧化应激
认知功能
热休克蛋白
dexmedetomidine
sepsis
oxidative stress
cognitive function
heat shock protein
