开滦总医院林西医院急诊科,河北 唐山 063000
Received:19 June 2024,
Published:25 July 2025
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张墨,尚杨,张俊娜等.仙茅苷对癫痫大鼠海马神经元损伤的影响机制研究[J].局解手术学杂志,2025,34(07):589-594.
ZHANG Mo,SHANG Yang,ZHANG Jun-na,et al.Study on the effect and mechanism of curculigoside on hippocampal neuron injury in epileptic rats[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2025,34(07):589-594.
张墨,尚杨,张俊娜等.仙茅苷对癫痫大鼠海马神经元损伤的影响机制研究[J].局解手术学杂志,2025,34(07):589-594. DOI: 10.11659/jjssx.06E024078.
ZHANG Mo,SHANG Yang,ZHANG Jun-na,et al.Study on the effect and mechanism of curculigoside on hippocampal neuron injury in epileptic rats[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2025,34(07):589-594. DOI: 10.11659/jjssx.06E024078.
目的
2
探究仙茅苷(CUR)对癫痫大鼠海马神经元损伤的影响机制。
方法
2
选取48只大鼠,采用35 mg/kg戊四氮诱导建立癫痫大鼠模型,并将癫痫大鼠随机分为癫痫组、癫痫+低剂量CUR组(癫痫+CUR-L组)、癫痫+高剂量CUR组(癫痫+CUR-H组)和癫痫+CUR-H+PI3K激活剂740Y-P组(癫痫+CUR-H+740Y-P组),每组12只;另取12只腹腔注射等量生理盐水的大鼠为对照组。给药4周后,观察各组大鼠的行为学变化。尼氏染色测定海马组织神经元变化,免疫组化法测定海马组织小胶质细胞数目,ELISA测定海马组织白细胞介素(IL)-6、IL-1β、γ氨基丁酸(GABA)水平,TUNEL染色分析海马组织神经元凋亡水平,Western blot测定海马组织PI3K、Akt、mTOR磷酸化水平。
结果
2
与对照组比较,癫痫组大鼠Racine等级评分、癫痫发作频率、海马组织小胶质细胞数目、IL-6水平、IL-1β水平、神经元凋亡率及p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR水平显著升高/增多(
P
<
0.05),海马组织GABA水平显著降低(
P
<
0.05),海马组织神经元排列紊乱,出现神经元丢失。与癫痫组比较,癫痫+CUR-L组、癫痫+CUR-H组大鼠Racine等级评分、癫痫发作频率、海马组织小胶质细胞数目、IL-6水平、IL-1β水平、神经元凋亡率及p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR水平显著降低/减少(
P
<
0.05),海马组织GABA水平显著升高(
P
<
0.05),海马组织神经元丢失及坏死减少,细胞排列有所改善。与癫痫+CUR-H组比较,癫痫+CUR-H+740Y-P组大鼠Racine等级评分、癫痫发作频率、海马组织小胶质细胞数目、IL-6水平、IL-1β水平、神经元凋亡率及p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR水平显著升高/增多(
P
<
0.05),海马组织GABA水平显著降低(
P
<
0.05),海马组织神经元丢失及坏死增多,且细胞排列紊乱。
结论
2
CUR可能通过下调PI3K/Akt/mTOR信号通路减轻癫痫大鼠海马神经元损伤。
Objective
2
To investigate the effect and mechanism of curculigoside (CUR) on hippocampal neuron injury in epileptic rats.
Methods
2
Forty-eight rats were selected,and the epileptic rat models were established by induction with 35 mg/kg pentylenetetrazol.The epileptic rats were randomly divided into the epilepsy group,the epilepsy+low-dose CUR group (the epilepsy+CUR-L group),the epilepsy+high-dose CUR group (the epilepsy+CUR-H group),and the epilepsy+CUR-H+PI3K activator 740Y-P group (the epilepsy+CUR-H+740Y-P group),with 12 rats in each group.Another 12 rats that were intraperitoneally injected with the same amount of normal saline were taken as the control group.Four weeks after administration,the behavioral changes of rats in each group were observed.Nissl staining was applied to determine the neuronal changes in hippocampal tissue.Immunohistochemistry was applied to detect the number of microglia in hippocampal tissue.ELISA was applied to detect the levels of interleukin-6 (IL-6),IL-1β,and gamma-aminobutyric acid (GABA) in hippocampal tissue.TUNEL staining was applied to analyze the level of neuronal apoptosis in hippocampal tissue.Western blot was applied to detect the phosphorylation levels of PI3K,Akt and mTOR in hippocampal tissue.
Results
2
Compared with the control group,the Racine score and the frequency of epileptic seizures in rats,and the number of microglia,level of IL-6,level of IL-1β,the apoptosis rate of neurons,and levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR in hippocampal tissue in the epilepsy group were obviously increased (
P
<
0.05),while the level of GABA in hippocampal tissue was obviously reduced (
P
<
0.05),and the arrangement of neurons in hippocampal tissue was disordered,with neuronal loss.Compared with the epilepsy group,the Racine score,and the frequency of epileptic seizures in rats,and the number of microglia,levels of IL-6,levels of IL-1β,the apoptosis rates of neurons,and levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR in hippocampal tissue in the epilepsy+CUR-L group and the epilepsy+CUR-H group were significantly decreased (
P
<
0.05),while the levels of GABA in hippocampus tissue were significantly increased (
P
<
0.05),the loss and necrosis of neurons in hippocampus tissue were decreased,and the disorder of cell arrangement was improved.Compared with the epileps
y+CUR-H group,the Racine score and the frequency of epileptic seizures in rats,and the number of microglia,level of IL-6,level of IL-1β,the apoptosis rate of neurons,and levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR in hippocampal tissue in the epilepsy+CUR-H+740Y-P group were significantly increased (
P
<
0.05),while the level of GABA in hippocampus tissue was significantly decreased (
P
<
0.05),the loss and necrosis of hippocampal neurons increased,and the cell arrangement was disordered.
Conclusion
2
CUR may reduce hippocampal neuron damage in epileptic rats by downregulating the PI3K/Akt/mTOR signaling pathway.
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