摘要
目的观察脂联素对脂多糖诱导脓毒症小鼠脑损伤的保护作用,并探索线粒体功能在其中发挥的作用。方法健康雄性C57BL/6小鼠84只,6~8月龄,体质量20~25g,采用数字表法随机分为4组,即空白对照组(CON组)、脂联素对照组(APN组)、脓毒症模型组(LPS组)和脂联素干预组(LPS+APN组)。应用旷场实验和跳台实验观察小鼠的行为学变化,进行HE染色观察海马病理形态学改变,提取海马线粒体检测ROS、MDA、SOD的表达,Western blot法检测海马Bcl-2、Bax、cleaved caspase-3蛋白表达。结果LPS组小鼠在旷场和跳台实验中表现出的学习记忆能力较对照组明显下降,使用脂联素干预后学习记忆能力有所改善;LPS组小鼠海马神经元结构遭到破坏,海马线粒体ROS和MDA含量增加、SOD水平降低,Bcl-2、Bax、cleaved caspase-3蛋白表达水平增加。使用脂联素干预后神经元结构紊乱减轻,线粒体相关的氧化应激和凋亡水平降低。结论线粒体损伤诱导的氧化应激和凋亡可能参与了脓毒症小鼠脑损伤,脂联素可能通过抑制线粒体损伤相关的氧化应激和凋亡来发挥神经保护以及改善认知作用。
Objective To investigate the protective effect of adiponectin on C57BL/6 mice with lipopolysaccharide-induced septic cerebral injury,and to explore the role of mitochondrial function in the mechanism of sepsis-associated cognitive dysfunction.Methods Healthy male C57BL/6 mice(n=84),aged 6-8months,weighing 20-25g,were randomly divided into 4 groups:control(CON)group,adiponectin(APN)group,sepsis model(LPS)group and adiponectin treatment(LPS+APN)group.The behavioral changes of the mice were observed using the open-field test and step-down test.HE staining was used to observe the morphology of hippocampal neurons.ROS,MDA content and SOD activity of mitochondria in hippocampal tissues were detected by the kit.Western blot was used to detect the expressions of Bcl-2,Bax and cleaved caspase-3 proteins.Results Compared with the control group,the learning and memory of the model mice in the open-field test and step-down test were signifiantly decreased,and the decline were reversed after adiponectin intervention.Meanwhile,the levels of Bcl-2,Bax and cleaved caspase-3 protein expressions and the percentage of apoptotic cells increased,accompanied with the increased ROS,MDA content,reduced SOD activity and destroyed hippocampal cell structure.In the adiponectin intervention group,less pronounced cell structure destruction,depressed mitochondria-associated apoptosis and oxidative stress levels were observed compared with the LPS group.Conclusion The mitochondria-associated oxidative stress and apoptosis may be involved in cognitive impairment in septic mice.Adiponectin probably plays a protective effect in improving the cognitive function by inhibiting the mitochondria-associated apoptosis and antioxidative stress.
作者
张占琴
王强
Zhang Zhanqin;Wang Qiang(Department of Anesthesiology,The First Affiiated Hospital of Xi′an Jiaotong University,Shaanxi 710061,China)
出处
《医学研究杂志》
2020年第5期41-45,52,共6页
Journal of Medical Research
基金
国家自然科学基金资助项目(81801958)
陕西省自然科学基础研究计划项目(一般项目)(青年)(2019JQ-352)。
关键词
脂联素
脓毒症脑损伤
线粒体
认知功能
Adiponectin
Septic cerebral injury
Mitochondria
Cognitive function