
浏览全部资源
扫码关注微信
1.广西壮族自治区人民医院中医科,南宁 530021
2.南宁市第二人民医院关节外科,南宁 530031
主治医师,硕士。研究方向:中西医结合脑病方向的临床与基础研究。E-mail:luling931101@163.com
主任医师,硕士。研究方向:中西医结合脑病方向的临床与基础研究。E-mail:1172184758@qq.com
收稿:2026-02-01,
修回:2026-06-17,
录用:2026-06-18,
纸质出版:2026-07-15
移动端阅览
卢玲,庄胜,覃一珏,等.加味小柴胡汤调控AKT/Bcl-xL/Bax/Caspase-3信号轴抑制癫痫小鼠海马神经元凋亡的机制研究[J].中国药房,2026,37(13):1728-1734.
LU Ling,ZHUANG Sheng,QIN Yijue,et al.Study on the mechanism of Jiawei xiaochaihu decoction inhibiting hippocampal neuronal apoptosis in epileptic mice via regulating AKT/Bcl-xL/Bax/Caspase-3 signaling axis[J].ZHONGGUO YAOFANG,2026,37(13):1728-1734.
卢玲,庄胜,覃一珏,等.加味小柴胡汤调控AKT/Bcl-xL/Bax/Caspase-3信号轴抑制癫痫小鼠海马神经元凋亡的机制研究[J].中国药房,2026,37(13):1728-1734. DOI: 10.6039/j.issn.1001-0408.2026.13.12.
LU Ling,ZHUANG Sheng,QIN Yijue,et al.Study on the mechanism of Jiawei xiaochaihu decoction inhibiting hippocampal neuronal apoptosis in epileptic mice via regulating AKT/Bcl-xL/Bax/Caspase-3 signaling axis[J].ZHONGGUO YAOFANG,2026,37(13):1728-1734. DOI: 10.6039/j.issn.1001-0408.2026.13.12.
目的
2
探讨加味小柴胡汤抑制急性癫痫模型小鼠海马神经元凋亡的作用机制。
方法
2
将36只雄性KM小鼠随机分为正常对照组(生理盐水)、癫痫模型组(生理盐水)、加味小柴胡汤组[7 g/(kg·d)]、卡马西平组[阳性对照,30 mg/(kg·d)],每组9只。除正常对照组外,其余各组小鼠均构建急性癫痫模型。造模成功后,各组小鼠连续灌胃相应药物/生理盐水2周,每天1次。给药结束后,观察小鼠海马CA1区超微结构及海马组织病理形态学变化,检测海马组织中TUNEL阳性细胞数以及蛋白激酶B(AKT)、胱天蛋白酶3(Caspase-3)、B细胞淋巴瘤-xL(Bcl-xL)、Bcl-2相关X蛋白(Bax)的表达水平和磷酸化AKT(p-AKT)/AKT比值。
结果
2
与正常对照组比较,癫痫模型组小鼠海马CA1区超微结构及病理损伤严重;海马组织中TUNEL阳性细胞数显著增加(
P
<0.05),p-AKT、Bcl-xL表达均显著下调(
P
<0.05),Bax、Caspase-3表达均显著上调(
P
<0.05),p-AKT/AKT比值显著降低(
P
<0.05)。与癫痫模型组比较,加味小柴胡汤组小鼠海马组织超微结构、病理损伤及上述各指标均显著改善(
P
<0.05)。
结论
2
加味小柴胡汤可抑制急性癫痫小鼠海马神经元凋亡;其机制可能与增强AKT磷酸化激活,提高p-AKT/AKT比值,上调Bcl-xL表达,下调Bax、Caspase-3表达有关。
OBJECTIVE
2
To explore the mechanism of Jiawei xiaochaihu decoction against hippocampal neuronal apoptosis in acute epileptic model mice.
METHODS
2
Thirty-six male KM mice were randomly divided into four groups with 9 mice in each group: normal control group (normal saline), epilepsy model group (normal saline), Jiawei xiaochaihu decoction group [7 g/(kg·d)] and carbamazepine group [positive control, 30 mg/(kg·d)]. Except for the normal control group, the acute epilepsy model was established in the other groups. After successful modeling, mice in each group were given corresponding drugs or normal saline by intragastric administration once a day for 2 consecutive weeks. After drug intervention, the ultrastructure and pathological morphology of hippocampal CA1 region were observed. The number of TUNEL-positive cells in hippocampus was detected, and the expression levels of protein kinase B (AKT), Caspase-3, B-cell lymphoma-extra large (Bcl-xL), Bcl-2-associated X protein (Bax), as well as the ratio of phosphorylated AKT(p-AKT) to AKT were determined.
RESULTS
2
Compared with the normal control group, severe ultrastructural and pathological damages were observed in the hippocampal CA1 region of epilepsy model group; the number of TUNEL-positive cells was significantly increased (
P
<0.05). The expression levels of p-AKT and Bcl-xL were significantly down-regulated (
P
<0.05), while the Bax and Caspase-3 were significantly up-regulated (
P
<0.05),accompanied by a remarkable decrease of p-AKT/AKT ratio (
P
<0.05). Compared with the epilepsy model group, hippocampal tissue ultrastructure, pathological damage, and the aforementioned indicators were significantly improved in Jiawei xiaochaihu decoction group (
P
<0.05).
CONCLUSIONS
2
Jiawei xiaochaihu decoction can inhibit hippocampal neuronal apoptosis in acute epileptic mice, and its mechanism may be related to activating AKT phosphorylation, increasing p-AKT/AKT ratio, up-regulating Bcl-xL expression and down-regulating the expression of Bax and Caspase-3.
Klein P , Kaminski R M , Koepp M , et al . New epilepsy therapies in development [J ] . Nat Rev Drug Discov , 2024 , 23 ( 9 ): 682 - 708 .
平鑫 , 秦少坤 , 刘书宁 , 等 . 难治性癫痫中西医诊治现状分析与临床对策 [J ] . 中华中医药杂志 , 2021 , 36 ( 2 ): 691 - 694 .
Sokolova T V , Zabrodskaya Y M , Litovchenko A V , et al . Relationship between neuroglial apoptosis and neuroinflammation in the epileptic focus of the brain and in the blood of patients with drug-resistant epilepsy [J ] . Int J Mol Sci , 2022 , 23 ( 20 ): 12561 .
汪倩 , 杨梅 , 赵琦 , 等 . 中药干预PI3K/AKT信号通路防治非酒精性脂肪性肝病研究现状 [J ] . 辽宁中医杂志 , 2025 , 52 ( 9 ): 209 - 213 .
Henshall D C , Simon R P . Epilepsy and apoptosis pathways [J ] . J Cereb Blood Flow Metab , 2005 , 25 ( 12 ): 1557 - 1572 .
丁黎敏 , 黄小民 , 张微 , 等 . 原花青素通过对Caspase-3和Bcl-xl、Bax蛋白的调节抑制人脐静脉内皮细胞凋亡 [J ] . 中华中医药学刊 , 2013 , 31 ( 3 ): 582 - 584 .
尤海玲 , 陈源 , 郭志英 . 小柴胡汤合桃核承气汤加味治疗海绵状血管瘤合并瘤内小灶出血及蛛网膜下腔出血并癫痫一例 [J ] . 环球中医药 , 2022 , 15 ( 8 ): 1437 - 1439 .
苏丽娟 , 王娟 , 刘旭恩 , 等 . 小柴胡汤抗抑郁作用及其对脑内神经递质、神经营养因子和雌性激素的影响研究 [J ] . 中华中医药学刊 , 2020 , 38 ( 9 ): 38 - 40 .
卢玲 , 李欢 , 廖现秋 , 等 . 小柴胡汤治疗癫痫的网络药理学研究 [J ] . 中国医院药学杂志 , 2020 , 40 ( 22 ): 2296 - 2302 .
刘应柯 , 李合国 , 宫璀璀 . 加味小柴胡汤对顺铂诱导的BRL细胞相关凋亡蛋白表达的影响 [J ] . 中国中医基础医学杂志 , 2009 , 15 ( 9 ): 665 - 667 .
汪顺贵 , 玉倩 , 李华霞 , 等 . 加味柴胡疏肝汤调控miR-204对急性癫痫小鼠海马AKT/mTOR/P70S6K通路和脑电图的影响 [J ] . 时珍国医国药 , 2020 , 31 ( 2 ): 273 - 276 .
Racine R J . Modification of seizure activity by electrical stimulation. Ⅱ. Motor seizure [J ] . Electroencephalogr Clin Neurophysiol , 1972 , 32 ( 3 ): 281 - 294 .
玉倩 , 汪顺贵 , 李华霞 , 等 . 从肝论治癫痫治疗进展 [J ] . 辽宁中医药大学学报 , 2020 , 22 ( 2 ): 118 - 121 .
Zhang S L , Liu N , Ma M X , et al . Methionine enkephalin (MENK) suppresses lung cancer by regulating the Bcl-2/Bax/caspase-3 signaling pathway and enhancing natural killer cell-driven tumor immunity [J ] . Int Immunopharmacol , 2021 , 98 : 107837 .
D’Orsi B , Kilbride S M , Chen G , et al . Bax regulates neuronal Ca 2+ homeostasis [J ] . J Neurosci , 2015 , 35 ( 4 ): 1706 - 1722 .
Chen Y B , Aon M A , Hsu Y T , et al . Bcl-xL regulates mitochondrial energetics by stabilizing the inner membrane potential [J ] . J Cell Biol , 2011 , 195 ( 2 ): 263 - 276 .
赖颖蓉 , 赵倩琳 , 姜丽红 . 基于Bcl-2/Bax/Caspase-3信号通路探究参红通络方对心肌缺血再灌注损伤大鼠细胞凋亡的影响 [J ] . 中国实验方剂学杂志 , 2024 , 30 ( 11 ): 104 - 110 .
Zhang F , Ru N , Shang Z H , et al . Daidzein ameliorates spinal cord ischemia/reperfusion injury-induced neurological function deficits in Sprague-Dawley rats through PI3K/Akt signaling pathway [J ] . Exp Ther Med , 2017 , 14 ( 5 ): 4878 - 4886 .
张家伟 , 许莉莉 , 吕佩源 . PI3K/AKT信号通路与缺血性脑损伤引起的细胞凋亡研究进展 [J ] . 临床与病理杂志 , 2022 , 42 ( 11 ): 2826 - 2831 .
Henshall D C , Araki T , Schindler C K , et al . Activation of Bcl-2-associated death protein and counter-response of Akt within cell populations during seizure-induced neuronal death [J ] . J Neurosci , 2002 , 22 ( 19 ): 8458 - 8465 .
Li X M , Liu Y , Wang S Y , et al . The polysaccharides from the aerial parts of Bupleurum chinens e DC attenuate epilepsy-like behavior through oxidative stress signaling pathways [J ] . Oxid Med Cell Longev , 2022 , 2022 : 7907814 .
Zuo H , Duan Z , Wang Z , et al . Gastrodin improves microglia-mediated inflammatory response after hypoxic-ischemic brain damage in neonatal rats via PI3K/AKT pathway [J ] . Nan Fang Yi Ke Da Xue Xue Bao , 2024 , 44 ( 9 ): 1712 - 1719 .
樊琼 , 邓小渝 , 傅继凡 , 等 . 黄芩苷通过PI3K/AKT/mTOR信号通路对人胶质瘤细胞凋亡与自噬的影响 [J ] . 中西医结合研究 , 2025 , 17 ( 4 ): 236 - 241 .
田艳 , 朱飞 , 宋采滢 , 等 . 党参多糖通过PI3K/AKT信号通路抑制瘢痕疙瘩成纤维细胞增殖和诱导细胞周期阻滞的实验研究 [J ] . 重庆医科大学学报 , 2024 , 49 ( 9 ): 1142 - 1146 .
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621