基于肾虚体质大鼠海马Ca^(+)信号异常表达探讨补肾中药改善学习记忆能力机制  

Mechanism of Kidney Tonifying Medicine on Improving Learning and Memory Ability During Abnormal Ca^(+) Regulatory Signal Expression in Hippocampus of Rats with Kidney Deficiency Constitution

作　　者：孙瑜嬬[1] 孙理军[1] 李翠娟[1] 张若珺 SUN Yuru;SUN Lijun;LI Cuijuan;ZHANG Ruojun(Shaanxi University of Chinese Medicine,Xianyang 712046,Shaanxi,China)

机构地区：[1]陕西中医药大学,陕西咸阳712046

出　　处：《辽宁中医药大学学报》2021年第5期26-30,共5页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：陕西省教育厅重点实验室研究项目(17JS033);陕西省科技厅研究项目(2018SF-312);陕西省中医药管理局中医藏象理论重点研究室建设项目(SZDYJS-2);陕西中医药大学中医经典理论研究创新团队建设项目(2019-YL01)。

摘　　要：目的通过肾虚体质大鼠海马区钙调神经磷酸酶(CaN)和钙蛋白酶1(Calpain-1)的异常表达,探讨补肾中药对肾虚体质大鼠学习记忆能力改善的调节机制。方法“猫吓鼠”造模法恐吓受孕母鼠至产子,将子代鼠(后称“仔鼠”)分为模型组、补肾组、补心组和疏肝组,并持续恐吓4周;恐吓的同时开始用药治疗12周;补肾组、补心组和疏肝组分别灌胃给予六味地黄丸、天王补心丹、逍遥丸0.9375 g·kg^(-1)·d^(-1);空白组仔鼠产自正常孕鼠,给予生理盐水对照。比较各组仔鼠生长发育情况,Morris水迷宫检测仔鼠学习记忆能力,免疫组化法检测海马区CaN、Calpain-1的阳性表达变化。结果Morris水迷宫实验,模型组与空白组比较,潜伏期和总路程增加(P<0.01);与模型组比较,补肾组潜伏期和总路程减少(P<0.01),补心组、疏肝组潜伏期减少(P<0.01);与补心组和疏肝组比较,补肾组潜伏期和总路程均减少(P<0.05)。对各组仔鼠称重并取脑组织称重,模型组仔鼠体质量、脑质量较空白组降低(P<0.01);中药治疗后,补肾组、补心组、疏肝组体质量、脑质量均较模型组升高(P<0.05);与疏肝组比较,补肾组体质量增高差异有统计学意义(P<0.05)。免疫组化实验结果显示,与空白组比较,模型组CaN、Calpain-1阳性细胞数升高(P<0.01);与模型组比较,补肾组、疏肝组CaN、Calpain-1阳性细胞数降低(P<0.05);与补心组比较,补肾组CaN、Calpain-1阳性细胞数降低(P<0.05)。结论实验结果证实,肾虚体质大鼠低下的学习记忆能力与海马区CaN、Calpain-1阳性表达升高有关。中药治疗后,补肾组、补心组、疏肝组通过降低CaN、Calpain-1的阳性表达,一定程度上改善了仔鼠的学习记忆能力。补肾组仔鼠通过补肾治疗直接改善肾脏功能,肾藏精、精生髓、髓通脑,故学习记忆能力的改善优于补心组和疏肝组,实验结果也证实了实验中肾虚体质动物模型构建的合理�Objective Through the abnormal expression of calcineurin(CaN)and Calpain-1 in the hippocampus of rats,to explore the regulatory effect of kidney tonifying medicine on learning and memory ability of rats with kidney deficiency constitution.Methods Using the method of“cat frighten mouse”to make the models,intimidated the pregnant mother rats and made them give birth.The offspring rats were divided into model group,kidney tonifying group,heart tonifying group and liver relaxing group.Continued to intimidate the offspring rats for 4 weeks,and started taking medicine at the same time.Liuwei Dihuang Pill(六味地黄丸),Tianwang Buxin Pill(天王补心丹)and Xiaoyao Pill(逍遥丸)were given 0.9375 g·kg^(-1)·d^(-1) respectively in kidney tonifying group,heart tonifying group and liver relaxing group.The rats in the blank group were born from normal pregnant rats and were given normal saline.The growth and development of each group were compared.Morris water maze was used to compare learning and memory ability.The expression of CaN and Calpain-1 was detected by immunohistochemistry.Results In Morris water maze experiment,compared with the blank group,the incubation period and total distance of the model group increased(P<0.01);Compared with the model group,the incubation period and total distance of the kidney tonifying group were reduced(P<0.01);The incubation period of heart tonifying group and liver relaxing group decreased(P<0.01);Compared with heart tonifying group and liver relaxing group,the incubation period and total distance of kidney tonifying group decreased(P<0.05).The weight and brain weight of the model group were lower than that of the blank group(P<0.01).After treatment,kidney tonifying group,heart tonifying group and liver relaxing group increased compared with the model group(P<0.05).Compared with liver relaxing group,the weight of kidney tonifying group increased(P<0.05).Compared with the blank group,the number of positive cells of CaN and Calpain-1 in the model group increased(P<0.01).Compar

关 键 词：肾虚体质 钙调神经磷酸酶 钙蛋白酶1 学习记忆能力 

分 类 号：R285.5[医药卫生—中药学]