中国药房2024，Vol.35Issue(9)：1050-1056,7.DOI:10.6039/j.issn.1001-0408.2024.09.05
脑震宁颗粒调节三重脑震荡大鼠线粒体能量代谢的机制研究
Mechanism of Naozhenning granules in regulating mitochondrial energy metabolism in multiple cerebral concussion rats
摘要
Abstract
OBJECTIVE To explore the mechanism of Naozhenning granules in regulating mitochondrial energy metabolism in hippocampal tissue of multiple cerebral concussion(MCC)model rats.METHODS SPF grade Wistar rats were used to prepare MCC models using the"free fall impact method".The successfully modeled rats were divided into model group,piracetam group,and Naozhenning granule low-dose,medium-dose and high-dose groups,and a normal group was also set up,with 8 rats in each group.Rats in each treatment group orally administered corresponding drugs at doses of 0.324 g/kg for the piracetam group and 2.25,4.5 and 9 g/kg for the Naozhenning granule low-dose,medium-dose and high-dose groups;the normal group and model group were given equal volumes of normal saline;once a day,for 14 consecutive days.The motor exploration ability,learning and memory ability of rats were tested;the adenosine triphosphate(ATP)content in the hippocampal tissue of rat was detected;the changes in the mitochondrial structure of hippocampal tissue was observed;the fluorescence intensity of mitochondrial dynamin-related protein 1(Drp1),mitochondrial fission protein 1(Fis1),mitochondrial fusion 1(Mfn1),and optic atrophy protein 1(Opa1)were detected in the hippocampal tissue of rat;the protein expression levels of peroxisome proliferator activated receptor gamma coactivator-1α(PGC-1α),nuclear respiratory factor-1(NRF-1),mitochondrial transcription factor A(TFAM),Wnt-3a,β-catenin in hippocampal tissue of rat were detected.RESULTS Compared with the normal group,the total exercise distance,number of central grid entries,number of upright positions,new object recognition index,mitochondrial ATP content,fluorescence intensity of Mfn1 and Opa1,the protein expression levels of PGC-1α、NRF-1、TFAM、Wnt-3a、β-catenin in the model group were significantly reduced(P＜0.01),while the rest time and fluorescence intensity of Drp1 and Fis1 in hippocampal tissue were significantly increased(P＜0.01).The results of transmission electron microscopy showed that the mitochondria in the hippocampal tissue were significantly swollen,with a large number of broken and reduced cristae,and some mitochondria had myeloid changes in the membrane.Compared with the model group,the levels/contents of the above indicators in rats of each administration group showed varying degrees of reversal,and most of the differences were statistically significant(P＜0.05 or P＜0.01);the degree of mitochondrial swelling in the hippocampal tissue was reduced,with a small amount of broken and reduced cristae,fuzzy fractures appeared in local areas of the rough endoplasmic reticulum.CONCLUSIONS Naozhenning granules can improve the motor exploration,learning and memory abilities of MCC model rats,repair neuronal damage,and exert neuroprotective effects.Its mechanism may be related to activating Wnt/β-catenin signaling pathway,maintaining the balance of mitochondrial division and fusion,and promoting mitochondrial biosynthesis.关键词
脑震宁颗粒/三重脑震荡/线粒体/Wnt/β-catenin信号通路/海马组织/神经保护Key words
Naozhenning granules/multiple cerebral concussion/mitochondrial/Wnt/β-catenin signaling pathway/hippocampal tissue/neuroprotection分类
医药卫生引用本文复制引用
高丽,赵乐,魏楠楠,武立雅,王恬恬,张唯依,王永辉..脑震宁颗粒调节三重脑震荡大鼠线粒体能量代谢的机制研究[J].中国药房,2024,35(9):1050-1056,7.基金项目
国家自然科学基金项目(No.82104972) （No.82104972）
山西省卫生健康委员会中医药重点研究室建设项目(No.zyyyjs2024023) （No.zyyyjs2024023）
山西省中医药管理局科研课题(No.2022ZYYC267) （No.2022ZYYC267）
山西中医药大学博士科研启动基金项目(No.2022BK19) （No.2022BK19）
山西中医药大学科技创新能力培育计划(No.2023PY-YS-03) （No.2023PY-YS-03）
