FKBP5在癫痫大鼠海马的表达及其与突触可塑性损伤的关联OA
Expression of FKBP5 in hippocampus of epileptic rats and its correlation with synaptic plasticity damage
目的 观察FK-506结合蛋白5(FK506 binding protein 5,FKBP5)在癫痫大鼠海马组织中的动态表达及其与突触可塑性损伤的关联.方法 将24只雄性SD大鼠随机分为对照组和模型组,每组12只.采用氯化锂-匹罗卡品腹腔注射的方法诱导癫痫模型,记录癫痫发作潜伏期.采用Racine等级标准评定癫痫急性发作等级,并记录皮层脑电图;qRT-PCR、Western blot方法检测海马组织FKBP5 mRNA及蛋白水平;高尔基染色观察海马神经元树突棘损伤情况;Western blot检测PSD95、BDNF、synapsin-1和synaptotagmin-1蛋白水平.结果 SD大鼠腹腔注射氯化锂-匹罗卡品后表现出典型的癫痫发作行为,并呈高波幅节律性棘波和尖波波形;与对照组相比,模型组大鼠海马FKBP5蛋白在癫痫发作1、4、24 h均明显升高(P<0.05),其中在24 h蛋白表达最高(P<0.01).癫痫发作24 h模型组大鼠海马神经元的树突棘密度、分支长度及突触可塑性相关蛋白表达均明显降低(P<0.05).Pearson相关性分析结果表明,FKBP5蛋白表达与PSD95、synaptotagmin-1 蛋白表达呈负相关(P<0.05).结论 氯化锂-匹罗卡品腹腔注射可成功诱导大鼠癫痫模型,海马FKBP5的表达改变参与癫痫大鼠海马突触可塑性损伤的发生机制.
Aim To observe the dynamic expression of FK-506 binding protein 5(FKBP5)in the hippo-campal tissue of epileptic rats and its correlation with synaptic plasticity damage.Methods Twenty-four male SD rats were randomly divided into a control group and a model group,with 12 rats in each group.The epileptic model was induced by intraperitoneal in-jection of lithium chloride-pilocarpine,and the seizure latency was recorded.The level of seizures was as-sessed according the Racine grading standard,and cortical electroencephalograms were recorded.The levels of FKBP5 mRNA and protein in hippocampal tis-sues were detected by qRT-PCR and Western blotting.Golgi staining was used to observe the damage of neu-ronal dendritic spines in the hippocampus.Western blot was used to detect the protein levels of PSD95,BDNF,synapsin-1,and synaptotagmin-1.Results SD rats showed typical epileptic seizure behaviors after intraperitoneal injection of lithium chloride-pilocarpine,accompanied by high-amplitude rhythmic spike and sharp wave patterns.Compared to the con-trol group,the hippocampal FKBP5 protein levels in the model group significantly increased at 1,4,and 24 h post-seizure(P<0.05),with the highest protein expression at 24 h(P<0.01).At 24 h post-seizure,the dendritic spine density,branch length and synap-tic plasticity-related protein expression in the hippo-campal neurons of the model group rats were signifi-cantly reduced(P<0.05).Pearson correlation analy-sis revealed that FKBP5 protein expression was signifi-cantly negatively correlated with the expression of PSD95 and synaptotagmin-1 proteins(P<0.05).Con-clusions Intraperitoneal injection of lithium chloride-pilocarpine can successfully induce epileptic models in rats,and the changed expression of FKBP5 in the hippocampus is involved in the mechanism underlying synaptic plasticity impairment in the hippocampus of epileptic rats.
王传玉;徐松林;葛金芳
安徽医科大学药学科学学院||炎症免疫性疾病安徽省实验室,安徽 合肥 230032安徽医科大学药学科学学院||炎症免疫性疾病安徽省实验室,安徽 合肥 230032安徽医科大学药学科学学院||炎症免疫性疾病安徽省实验室,安徽 合肥 230032
医药卫生
癫痫FKBP5突触可塑性匹罗卡品神经炎症认知
epilepsyFKBP5synaptic plastictypi-locarpineneuroinflammationcognition
《中国药理学通报》 2026 (2)
247-254,8
安徽省高校协同创新项目(No GXXT-2020-062)
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