补肾中药对肾虚质大鼠海马区ERK1表达的影响
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摘要
目的观察补肾中药对肾虚质大鼠学习记忆能力及海马区ERK1蛋白表达的影响,从突触可塑性角度探讨其改善肾虚体质学习记忆能力的内在分子机制。方法采用"猫吓鼠"造模法构建先天不足加后天恐吓型肾虚质大鼠模型,分为模型组、补肾组、补心组、疏肝组4组,补肾组、补心组、疏肝组分别予以六味地黄丸、天王补心丹、逍遥丸,空白组产自正常孕鼠。Morris水迷宫实验检测各组大鼠学习记忆能力;称取体重、脑重比较生长发育情况;免疫组化法检测海马ERK1阳性细胞表达。结果与空白组比较,模型组总路程显著增加,30s内目标区域停留时间、体重、脑重及海马区ERK1阳性表达显著减少;与模型组比较,补肾组、补心组、疏肝组总路程均显著减少,30s内目标区域停留时间、体重、脑重及海马区ERK1阳性表达显著增加;与补心组、疏肝组比较,补肾组总路程显著减少,30s内目标区域停留时间、体重、脑重及海马区ERK1阳性表达显著增加。结论补肾中药可通过提高海马区学习记忆蛋白ERK1的表达对肾虚质大鼠学习记忆力起治疗作用;海马区ERK1表达变化与肾藏志理论具有相关性。
Objective:To observe the effect of kidney-invigorating herbs on learning and memory ability and expression of ERK1 protein in hippocampus of rats with kidney-deficiency syndrome,and to explore the intrinsic molecular mechanism of improving learning and memory ability of kidney-deficiency syndrome from the perspective of synaptic plasticity.Method:The rat model of congenital insufficiency and acquired intimidation of kidney deficiency was established by " cat scare rat" model.The rats were divided into four groups:model group,kidney-invigorating group,heart-tonifying group and liver-soothing group.The kidney-invigorating group,heart-tonifying group and liver-soothing group were given Liuwei Dihuang Pills,Tianwang Buxin Bolus and Xiaoyao pills respectively.The blank group was produced from normal pregnant rats.Morris water maze test was used to test the learning and memory abilities of rats in each group.The body weight and brain weight were used to compare the growth and development.The expression of ERK1 positive cells in hippocampus was detected by immunohistochemistry.Result:Compared with the blank group,the total distance of the model group increased significantly.The target area retention time,body weight,brain weight and ERK1 positive expression in the hippocampus were significantly reduced within 30 s.Compared with the model group,the total distance of the kidney-invigorating group,heart-tonifying group and liver-soothing group were all significantly decreased,the target area retention time,body weight,brain weight and hippocampus ERK1 positive expression increased significantly within 30 s;Compared with the heart-tonifying group and liver-soothing group,the total distance of kidney-invigorating group decreased significantly,and the retention time,body weight,brain weight and positive expression of ERK1 in hippocampus increased significantly in 30 seconds.Conclusion:Kidney-invigorating herbs can improve the learning and memory of rats with kidney deficiency by increasing the expression of learning memory protein ERK1 in hippocampus;the expression of ERK1 in hippocampus is related to the theory of "kidney storing will".
Objective:To observe the effect of kidney-invigorating herbs on learning and memory ability and expression of ERK1 protein in hippocampus of rats with kidney-deficiency syndrome,and to explore the intrinsic molecular mechanism of improving learning and memory ability of kidney-deficiency syndrome from the perspective of synaptic plasticity.Method:The rat model of congenital insufficiency and acquired intimidation of kidney deficiency was established by " cat scare rat" model.The rats were divided into four groups:model group,kidney-invigorating group,heart-tonifying group and liver-soothing group.The kidney-invigorating group,heart-tonifying group and liver-soothing group were given Liuwei Dihuang Pills,Tianwang Buxin Bolus and Xiaoyao pills respectively.The blank group was produced from normal pregnant rats.Morris water maze test was used to test the learning and memory abilities of rats in each group.The body weight and brain weight were used to compare the growth and development.The expression of ERK1 positive cells in hippocampus was detected by immunohistochemistry.Result:Compared with the blank group,the total distance of the model group increased significantly.The target area retention time,body weight,brain weight and ERK1 positive expression in the hippocampus were significantly reduced within 30 s.Compared with the model group,the total distance of the kidney-invigorating group,heart-tonifying group and liver-soothing group were all significantly decreased,the target area retention time,body weight,brain weight and hippocampus ERK1 positive expression increased significantly within 30 s;Compared with the heart-tonifying group and liver-soothing group,the total distance of kidney-invigorating group decreased significantly,and the retention time,body weight,brain weight and positive expression of ERK1 in hippocampus increased significantly in 30 seconds.Conclusion:Kidney-invigorating herbs can improve the learning and memory of rats with kidney deficiency by increasing the expression of learning memory protein ERK1 in hippocampus;the expression of ERK1 in hippocampus is related to the theory of "kidney storing will".
引文
[1]孙理军,孙耀光,张琪,等.肾虚质大鼠生长发育和学习记忆能力与肾藏志理论相关性研究[J].中华中医药杂志,2016,31(1):36-38.
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[6]范新六.基于突触可塑性的加味四逆散对睡眠剥夺大鼠学习记忆障碍的调控机制研究[D].北京:北京中医药大学,2011.
[7]胡亚卓,吕佩源. MAPK/ERK信号转导通路与学习记忆[J].中国神经免疫学和神经病学杂志,2006,13(6):369-372.
[8]周霞.健忘证防治方药的中医文献研究[D].山东:山东中医药大学,2002.
[9]贺文彬.肾阳虚对海马突触可塑性的影响[D].济南:山东中医药大学,2007.
[10]施新猷.现代医学实验动物学[M].北京:人民军医出版社,2000:332-335.
[11]胡亚卓,吕佩源. MAPK/ERK信号转导通路与学习记忆[J].中国神经免疫学和神经病学杂志,2006,13(6):369-372.
[12]方向.基于突触可塑性和MAPK/ERK信号通路的清热利胆解毒方对铜负荷大鼠学习记忆行为的干预机制研究[D].武汉:湖北中医药大学,2013.
[13]Silva AJ,Frankland PW,Marowitz Z,etal. A mouse model for the learning and memory deficits associated with neurofibromatosis type I[J]. Nat Genet,1997,15(3):281-284.
[14]刘永惠,李少为,郑清莲.补肾健脑方对血管性痴呆大鼠乙酰胆碱和海马区ERK1和ERK2表达的影响[J].中国中西医结合杂志,2012,32(4):504-509.
[2]房玲,樊永平,王蕾.六味地黄丸(汤)的临床应用研究[J].中华中医药杂志,2013,28(7):2181-2185.
[3]孙瑜嬬,孙理军,孙耀光,等.补肾中药对肾虚质大鼠生长发育及脑组织胆碱乙酰化酶含量的影响[J].中国中医药信息杂志,2017,24(9):48-50.
[4]孙理军,孙耀光,孙瑜嬬,等.基于SNAP-25表达的肾虚质大鼠突触可塑性实验研究[J].中国中医基础医学杂志,2017,23(9):1217-1219,1279.
[5]孙理军,孙耀光,孙瑜嬬,等.肾虚质大鼠生长发育与蛋白激酶C表达的研究[J].中华中医药杂志,2018,33(3):1134-1136.
[6]范新六.基于突触可塑性的加味四逆散对睡眠剥夺大鼠学习记忆障碍的调控机制研究[D].北京:北京中医药大学,2011.
[7]胡亚卓,吕佩源. MAPK/ERK信号转导通路与学习记忆[J].中国神经免疫学和神经病学杂志,2006,13(6):369-372.
[8]周霞.健忘证防治方药的中医文献研究[D].山东:山东中医药大学,2002.
[9]贺文彬.肾阳虚对海马突触可塑性的影响[D].济南:山东中医药大学,2007.
[10]施新猷.现代医学实验动物学[M].北京:人民军医出版社,2000:332-335.
[11]胡亚卓,吕佩源. MAPK/ERK信号转导通路与学习记忆[J].中国神经免疫学和神经病学杂志,2006,13(6):369-372.
[12]方向.基于突触可塑性和MAPK/ERK信号通路的清热利胆解毒方对铜负荷大鼠学习记忆行为的干预机制研究[D].武汉:湖北中医药大学,2013.
[13]Silva AJ,Frankland PW,Marowitz Z,etal. A mouse model for the learning and memory deficits associated with neurofibromatosis type I[J]. Nat Genet,1997,15(3):281-284.
[14]刘永惠,李少为,郑清莲.补肾健脑方对血管性痴呆大鼠乙酰胆碱和海马区ERK1和ERK2表达的影响[J].中国中西医结合杂志,2012,32(4):504-509.