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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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| 篇名： | 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 |
| TITLE： | Effect and mechanism of Buyang huanwu decoction on mitochondrial dynamics in rats with cerebral ischemia-reperfusion injury |
| 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3.15mg/kg）组、高剂量BYHWD（H-BYHWD，灌胃12.60mg/kg）组、阳性对照（腹腔注射150mg/kg银杏叶提取物注射液）组、H-BYHWD+溶剂对照（灌胃12.60mg/kgBYHWD+腹腔注射20mg/kg二甲基亚砜）组、H-BYHWD+CompoundC（灌胃12.60mg/kgBYHWD+腹腔注射20mg/kgCompoundC）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+CompoundC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。 |
| 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 group， H-BYHWD group， and positive control group， M025） compared with the CIRI group （P＜0.05）. Compared with the H-BYHWD group and H-BYHWD+solvent control group， the above indicators of rats in the H-BYHWD+Compound C group showed significant reversal（P＜0.05）. There was no statistically significant difference in the above indicators between the H-BYHWD+solvent control group and the H-BYHWD group （P＞0.05）. CONCLUSIONS BYHWD may improve CIRI by activating the AMPK/Drp1 pathway and ameliorating mitochondrial dynamic disorders. |
| 期刊： | 2025年第36卷第23期 |
| 作者： | 张雯；杨畅；金海涛 |
| AUTHORS： | ZHANG Wen，YANG Chang，JIN Haitao |
| 关键字： | 补阳还五汤；脑缺血再灌注损伤；AMPK/Drp1通路；线粒体动力学 |
| KEYWORDS： | Buyang huanwu decoction； cerebral ischemia-reperfusion injury； AMPK/Drp1 pathway； mitochondrial dynamics |
| 阅读数： | 1 次 |
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