脑震宁颗粒对三重脑震荡模型大鼠额颞叶皮质区线粒体生物合成的影响  

Effect of Naozhenning Granules on Energy Metabolism of Cortical Mitochondria in Rat Model of Post-concussion Syndrome

作　　者：魏楠楠 武立雅 王恬恬 刘骐肇 张唯依 王永辉 高丽 赵乐 WEI Nannan;WU Liya;WANG Tiantian;LIU Qizhao;ZHANG Weiyi;WANG Yonghui;GAO Li;ZHAO Le(Shanxi University of Chinese Medicine,Jinzhong 030619,China)

机构地区：[1]山西中医药大学,山西晋中030619

出　　处：《中国实验方剂学杂志》2024年第14期107-113,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(82104972);山西省中医药管理局项目(2022ZYYC267);山西中医药大学博士科研启动基金项目(2022BK19);山西中医药大学科技创新能力培育计划项目(2023PY-YS-03)。

摘　　要：目的:基于线粒体能量代谢,从生物合成角度探究脑震宁颗粒对脑震荡后综合征模型大鼠的记忆功能和神经元的影响。方法:SPF级Wistar大鼠,采用自由落体撞击法构建三重脑震荡模型(MCC),依据模型评价标准将造模成功大鼠分为模型组,吡拉西坦组(0.324 g·kg^(-1)),脑震宁低、中、高剂量组(2.25、4.5、9 g·kg^(-1)),另设正常组,按剂量进行灌胃治疗,正常组和模型组给予等体积生理盐水,每天1次,连续14 d。观察大鼠给药前后的一般状态;采用旷场实验和新物体识别实验检测大鼠的运动和记忆能力;采用苏木素-伊红(HE)染色观察大鼠皮层组织神经元的病理改变;采用蛋白免疫印迹法(Western blot)和实时荧光定量聚合酶链式反应(Real-time PCR)检测大鼠组织过氧化物酶体增殖物激活受体γ-共激活因子-1α(PGC-1α)、核呼吸因子1(NRF-1)、线粒体转录因子(TFAM)的蛋白和mRNA表达。结果:与正常组比较,模型组大鼠精神焦虑狂躁,被毛萎黄脏乱,摄食量减少;旷场实验中模型大鼠的运动总路程、中央格进入次数和直立次数显著降低(P<0.01),静止时间显著升高(P<0.01);新物体识别指数显著下降(P<0.01);皮层组织神经元数量减少,分布稀疏,核仁畸形、破裂,形态不规则;皮层组织PGC-1α、NRF-1、TFAM的蛋白表达水平均显著降低(P<0.01);皮层组织PGC-1α、NRF-1、TFAM的mRNA表达水平均显著降低(P<0.01)。与模型组比较,吡拉西坦组和脑震宁各剂量组大鼠精神状态和被毛颜色改善,食欲增加,活动逐渐正常;旷场实验中大鼠的运动总路程、中央格进入次数和直立次数明显增高(P<0.05,P<0.01),静止时间明显降低(P<0.05,P<0.01);新物体识别指数明显上升(P<0.05,P<0.01);皮层组织神经元数量增多,排列较为紧密,核大而圆,部分细胞形态不规则,胞浆浑浊;吡拉西坦组和脑震宁中剂量组皮层组织PGC-1α、NRF-1和TFAM蛋白表达显著升高(P<0.01),脑震宁低�Objective:To explore the effects of Naozhenning granules on the memory function and neuron cells in the rat model of post-concussion syndrome based on mitochondrial biosynthesis.Method:SPFgrade Wistar rats were used to establish the multiple cerebral concussion(MCC)model by the weight-drop method.The successfully modeled rats were assigned into model,piracetam(0.324 g·kg^(-1)),and low-,medium-,and high-dose(2.25,4.5,and 9 g·kg^(-1),respectively)Naozhenning groups.The rats were administrated with corresponding drugs by gavage and those in the blank group and model group were administrated the same volume of normal saline once a day for 14 days.The general state of rats was observed before and after treatment.The open field test and new object recognition test were conducted to examine the motor and memory abilities of rats.Hematoxylin-eosin staining was employed to observe the pathological changes of cortical neurons in rats.Western blot and real-time polymerase chain reaction were employed to determine the protein and mRNA levels,respectively,of peroxisome proliferator-activated receptorγ-coactivator-1α(PGC-1α),nuclear respiratory factor-1(NRF-1),and transcription factor A mitochondrial(TFAM)in rat cortex.Result:Compared with the blank group,the model group showed anxious and manic mental status,yellow and messy fur,and reduced food intake.In the open field experiment,the model group showed reduced total movement distance,times of entering the central grid,and times of rearing decreased and increased resting time compared with the blank group(P<0.01).The model group had lower recognition index of new objects than the blank group(P<0.01).In addition,the modeling caused reduced neurons with sparse distribution and deformed,broken,and irregular nucleoli and down-regulated the mRNA and protein levels of PGC-1α,NRF-1,and TFAM in the cortex(P<0.01).Compared with the model group,piracetam and Naozhenning improved the mental state,coat color,food intake,and activities of rats.In the open field test,piracetam and Na

关 键 词：脑震荡后综合征 线粒体能量代谢 生物合成 脑震宁颗粒 皮层 

分 类 号：R284.2[医药卫生—中药学] R285[医药卫生—中医学] R289R287R22R2-031R33R24