Page 72 - 《中国药房》2025年23期

补阳还五汤对脑缺血再灌注大鼠线粒体动力学的影响及机制
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张 雯 ，杨 畅，金海涛（武汉市中医医院脑病科，武汉 430061）
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中图分类号 R965；R285 文献标志码 A 文章编号 1001-0408（2025）23-2946-06
DOI 10.6039/j.issn.1001-0408.2025.23.11

摘 要 目的 探究补阳还五汤（BYHWD）对脑缺血再灌注损伤（CIRI）大鼠线粒体动力学的影响及机制。方法 将CIRI大鼠随机
分为CIRI组、低剂量BYHWD（L-BYHWD，灌胃3.15 mg/kg）组、高剂量BYHWD（H-BYHWD，灌胃12.60 mg/kg）组、阳性对照（腹
腔注射 150 mg/kg 银杏叶提取物注射液）组、H-BYHWD+溶剂对照（灌胃 12.60 mg/kg BYHWD+腹腔注射 20 mg/kg 二甲基亚砜）
组、H-BYHWD+Compound C（灌胃12.60 mg/kg BYHWD+腹腔注射20 mg/kg Compound C）组，每组15只；另取15只大鼠作为假手
术组。各组大鼠灌胃或腹腔注射相应药液或生理盐水，每日1次，连续4周。末次给药后，检测大鼠脑梗死体积，观察缺血性半暗
带（IP）区内皮细胞线粒体超微结构，评估IP区线粒体膜电位，检测IP区视神经萎缩蛋白1（OPA1）与分化簇31（CD31）荧光共定位
面积比，线粒体融合蛋白2（MFN2）、OPA1、线粒体分裂蛋白1（Fis1）蛋白表达水平和AMP活化蛋白激酶（AMPK）/动力相关蛋白1
（Drp1）通路相关蛋白表达水平。结果 与假手术组比较，CIRI组大鼠脑组织IP区内皮细胞线粒体肿胀且多呈球状，嵴发生断裂且
空泡现象严重；脑梗死体积百分比、Fis1 蛋白表达水平及 Drp1 磷酸化水平均显著升高（P＜0.05），IP 区线粒体膜电位、OPA1 与
CD31 荧光共定位面积比和 MFN2、OPA1 蛋白表达水平及 AMPK 磷酸化水平均显著降低（P＜0.05）；与 CIRI 组比较，L-BYHWD
组、H-BYHWD组、阳性对照组大鼠上述指标均显著改善（P＜0.05）；与H-BYHWD组、H-BYHWD+溶剂对照组比较，H-BYHWD+
Compound C组大鼠上述指标均显著逆转（P＜0.05）；H-BYHWD+溶剂对照组与H-BYHWD组大鼠上述指标的差异均无统计学意
义（P＞0.05）。结论 BYHWD可通过激活AMPK/Drp1通路，改善线粒体动力学紊乱，从而改善CIRI。
关键词 补阳还五汤；脑缺血再灌注损伤；AMPK/Drp1通路；线粒体动力学

Effect and mechanism of Buyang huanwu decoction on mitochondrial dynamics in rats with cerebral
ischemia-reperfusion injury
ZHANG Wen，YANG Chang，JIN Haitao（Dept. of Encephalopathy， Wuhan Hospital of Traditional Chinese
Medicine， Wuhan 430061， China）

ABSTRACT OBJECTIVE To explore the effect and mechanism of Buyang huanwu decoction （BYHWD） on mitochondrial
dynamics in rats with cerebral ischemia-reperfusion injury （CIRI）. METHODS CIRI rats were randomly divided into CIRI group，
low-dose BYHWD （L-BYHWD， intragastric administration of 3.15 mg/kg BYHWD） group， high-dose BYHWD （H-BYHWD，
intragastric administration of 12.60 mg/kg BYHWD） group， positive control （intraperitoneal administration of 150 mg/kg Extract of
Ginkgo biloba leaves injection） group， H-BYHWD+solvent control （intragastric administration of 12.60 mg/kg BYHWD+
intraperitoneal injection of 20 mg/kg DMSO） group and H-BYHWD+Compound C （intragastric administration of 12.60 mg/kg
BYHWD+intraperitoneal injection of 20 mg/kg Compound C） group， with 15 rats in each group. Additionally， 15 rats were
assigned to the sham operation group. All rats received the corresponding medications or saline solution via intragastric
administration or intraperitoneal injection once daily for 4 consecutive weeks. After the last administration， the cerebral infarct
volume of rats was measured； the ultrastructure of mitochondria in endothelial cells in the ischemic penumbra （IP） region was
observed； the mitochondrial membrane potential was evaluated； the fluorescence colocalization area ratio of optic atrophy 1
（OPA1） to cluster of differentiation 31 （CD31） in the IP region was detected； the expressions of mitofusin 2 （MFN2）， OPA1，
mitochondrial fission 1 protein （Fis1）， and proteins related to the AMP-activated protein kinase （AMPK）/dynamin-related protein 1
（Drp1） pathway in the IP region were determined. RESULTS Compared with the sham operation group， mitochondria in
endothelial cells of the IP region in brain tissue of rats in the CIRI group were swollen， mostly spherical， with fractured cristae and
severe vacuolation； the percentage of cerebral infarct volume， Fis1 expression level and phosphorylation level of Drp1 were
increased significantly （P＜0.05）， while mitochondrial membrane potential in the IP region， fluorescence colocalization area ratio
of OPA1 to CD31， the expressions levels of MFN2 and OPA1， and phosphorylation level of AMPK were significantly decreased
（P＜0.05）. These indicators were improved in the L-BYHWD
Δ 基金项目 湖北省中医药管理局中医药科研项目（No.ZY2025-
group， H-BYHWD group， and positive control group，
M025）
＊第一作者 副主任医师，硕士。研究方向：中西医结合治疗神经 compared with the CIRI group （P＜0.05）. Compared with the
系统疾病。E-mail：r82emj@163.com H-BYHWD group and H-BYHWD+solvent control group， the
# 通信作者 副主任医师，硕士。研究方向：中西医结合治疗神经 above indicators of rats in the H-BYHWD+Compound C group
系统疾病。E-mail：562354@163.com showed significant reversal （P＜0.05）. There was no

· 2946 · China Pharmacy 2025 Vol. 36 No. 23 中国药房 2025年第36卷第23期