首页|RhoA/Cofilin信号通路在慢性铝中毒大鼠学习记忆及突触相关蛋白表达中的作用机制

RhoA/Cofilin信号通路在慢性铝中毒大鼠学习记忆及突触相关蛋白表达中的作用机制

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目的 研究RhoA/Cofilin信号通路在慢性铝中毒大鼠海马和大脑皮层中突触相关蛋白表达及学习记忆功能的调控作用.方法 根据大鼠每天体重,配置浓度为20 mmol/L的麦芽酚铝溶液,按20 μmol/kg对大鼠腹腔注射2个月建立慢性铝中毒大鼠模型,将慢性铝中毒模型大鼠随机分为2个组,即模型组、RhoA抑制剂组,RhoA抑制剂组用40 mg/kg的Rhosin盐酸盐腹腔注射,每天给药1次,连续30 d;另设空白对照组,每组各5只.用Morris水迷宫定位航行实验记录大鼠找到平台的游泳路径轨迹,Western Blot分别检测RhoA、Cofilin、突触素(SYN)、突触后致密蛋白(PSD-95)在海马组织和大脑皮层中的表达水平.结果 Morris水迷宫定位航行实验结果显示,与空白对照组比较,模型组大鼠运动轨迹趋向性较差,偏离目标平台;与模型组比较,RhoA抑制剂组大鼠运动轨迹更多趋向于目标平台.Western Blot结果显示,铝中毒模型组海马组织和大脑皮层的Cofilin、PSD-95、SYN蛋白相对表达量均比空白对照组的明显降低(P<0.05);铝中毒模型组海马组织和大脑皮层的RhoA蛋白相对表达量均比空白对照组的明显升高(P<0.01);RhoA抑制剂组海马组织和大脑皮层的Cofilin、PSD-95、SYN蛋白相对表达量均比铝中毒模型组的明显升高(P<0.05);RhoA抑制剂组海马组织和大脑皮层的RhoA蛋白相对表达量均比铝中毒模型组的明显降低(P<0.05).结论 通过抑制RhoA/Cofilin信号通路可以改善慢性铝中毒大鼠的学习记忆能力,可能与通过上调海马组织和大脑皮层中RhoA、SYN和PSD-95蛋白表达和下调海马组织和大脑皮层中Cofilin蛋白表达有关.
The mechanism of RhoA/Cofilin signaling pathway in learning and memory and the expression of synaptic-related proteins in rats with chronic aluminum poisoning
Objective To investigate the regulatory effect of RhoA/Cofilin signaling pathway on synaptic-related protein expression and learning and memory function in hippocampus and cerebral cortex of rats with chronic aluminum poisoning.Methods A chronic aluminum poisoning model rat was established by intraper-itoneal injection of a 20 mmol/L maltol aluminum solution at a dose of 20 μmol/kg per day for 2 months,based on the daily body weight of the rats.The rat models of chronic aluminum poisoning were randomly divided into two groups:a model group and a RhoA inhibitor group.The RhoA inhibitor group received intraperitoneal in-jections of 40 mg/kg Rhosin hydrochloride once daily for 30 consecutive days.An additional blank control group was included,with 5 rats in each group.The Morris water maze positioning navigation experiment was used to record the swimming paths of the rats to find the platform.Western Blot analysis was performed to de-tect the expression levels of RhoA,Cofilin,synaptophysin(SYN),and postsynaptic density protein 95(PSD-95)in the hippocampus and cerebral cortex.Results The results of Morris water maze positioning navigation experiment showed that compared with the blank control group,the rats in the model group exhibited poorer trajectory orientation and deviated from the target platform.Compared with the model group,the movement trajectory of rats in the RhoA inhibitor group was more inclined to the target platform.Western Blot results showed that the relative expression levels of Cofilin,PSD-95,and SYN proteins in the hippocampal tissue and cerebral cortex of the aluminum poisoning model group were significantly lower than those of the blank control group(P<0.05).The relative expression level of RhoA protein in the hippocampal tissue and cerebral cortex of the aluminum poisoning model group was significantly higher than that of the blank control group(P<0.01).The relative expression levels of Cofilin,PSD-95,and SYN proteins in the hippocampal tissue and cere-bral cortex of the RhoA inhibitor group were significantly higher than those of the aluminum poisoning model group(P<0.05).The relative expression level of RhoA protein in the hippocampal tissue and cerebral cortex of the RhoA inhibitor group was significantly lower than that of the aluminum poisoning model group(P<0.05).Conclusion Inhibiting the RhoA/Cofilin signaling pathway can improve the learning and memory a-bilities of rats with chronic aluminum poisoning,which may be related to the up-regulation of the expression of RhoA,SYN,and PSD-95 proteins and the down-regulation of the expression of Cofilin protein in the hipp-ocampal tissue and cerebral cortex.

RhoA/Cofilin signaling pathwayaluminum maltolchronic aluminum poisoninglearning and memory abilitiessynaptic-related proteins

刘文静、郭健雄、王小义、程厚之、张丽凤、廖素婵、李艳丽、黄俊杰

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右江民族医学院基础医学院,广西 百色 533000

RhoA/Cofilin信号通路 麦芽酚铝 慢性铝中毒 学习记忆能力 突触相关蛋白

2024

右江民族医学院学报
右江民族医学院

右江民族医学院学报

影响因子:0.708
ISSN:1001-5817
年,卷(期):2024.46(6)