目的 基于Ras相关C3肉毒素底物1（Ras-related C3 botulinum toxin substrate 1，Rac1）/蛋白激酶B（protein kinase B，Akt）/核因子-κB（nuclear factor-κB，NF-κB）通路探讨毛蕊花糖苷联合电针对缺血性脑卒中（ischemic stroke，IS）大鼠神经炎症及脑组织损伤的影响。方法 采用大脑中动脉栓塞方法构建IS大鼠模型，将造模成功的大鼠随机分为模型组、毛蕊花糖苷（10 mg/kg）组、电针组、毛蕊花糖苷＋电针组、尼莫地平（10 mg/kg）组、Rac1/Akt/NF-κB通路激活剂佛波酯（phorbol 12-myristate 13-acetate，PMA，10 μg/kg）组和毛蕊花糖苷＋电针＋PMA组，每组10只。另取10只正常大鼠作为对照组。造模成功后2 h，各给药组开始干预，持续治疗14 d。评估各组大鼠神经功能缺损及脑梗死面积；检测大鼠脑组织白细胞介素-17（interleukin-17，IL-17）、IL-1β和单核细胞趋化蛋白-1（monocyte chemoattractant protein-1，MCP-1）水平；检测大鼠脑组织病理损伤及细胞凋亡情况；检测大鼠脑组织S100β、精氨酸酶-1（arginase-1，Arg-1）以及Rac1/Akt/NF-κB通路相关蛋白表达。结果 与对照组比较，模型组大鼠神经功能损伤严重程度评分（neurological severity score，NSS）和脑梗死面积比显著升高（P＜0.05），脑组织IL-17、IL-1β和MCP-1水平显著升高（P＜0.05），脑组织病理损伤严重，细胞凋亡率显著升高（P＜0.05），脑组织S100β、Rac1、p-Akt/Akt、p-NF-κB p65/NF-κB p65蛋白表达水平显著升高（P＜0.05），Arg-1表达显著降低（P＜0.05）；与模型组比较，毛蕊花糖苷组、电针组、尼莫地平组、毛蕊花糖苷＋电针组以上指标均得到显著改善（P＜0.05），其中毛蕊花糖苷＋电针组改善效果显著优于毛蕊花糖苷组、电针组（P＜0.05）；PMA可以显著逆转毛蕊花糖苷联合电针对IS大鼠的改善作用（P＜0.05）。结论 毛蕊花糖苷联合电针可能通过抑制Rac1/Akt/NF-κB通路，改善IS大鼠神经炎症及脑组织损伤。

Objective To explore the effects of verbascoside combined with electroacupuncture on neuroinflammation and brain tissue damage in ischemic stroke (IS) rats based on Ras-related C3 botulinum toxin substrate 1 (Rac1)/protein kinase B (Akt)/nuclear factor-κB (NF-κB) pathway. Methods A rat model of IS was constructed using middle cerebral artery occlusion. The successfully modeled rats were randomly divided into model group, verbascoside (10 mg/kg) group, electroacupuncture group, averbascoside + electroacupuncture group, nifedipine (10 mg/kg) group, Rac1/Akt/NF-κB pathway activator phorbol 12-myristate 13-acetate (PMA, 10 μg/kg) group and verbascoside + electroacupuncture + PMA group, with 10 rats in each group. Another 10 normal rats were selected as the control group. After 2 h of successful modeling, each treatment group began intervention and continued treatment for 14 d. The neurological deficit and cerebral infarction area of rats in each group were evaluated. The levels of interleukin-17 (IL-17), IL-1β and monocyte chemoattractant protein-1 (MCP-1) in brain tissue of rats were detected. The pathological damage and cell apoptosis in brain tissue of rats were detected. The expressions of S100β, arginase-1 (Arg-1) and Rac1/Akt/NF-κB pathway related proteins in brain tissue of rats were detected. Results Compared with control group, the neurological severity score (NSS) and cerebral infarction area ratio of rats in model group were significantly increased (P < 0.05), the levels of IL-17, IL-1β and MCP-1 in brain tissue were significantly increased (P < 0.05), the pathological damage in brain tissue was severe, the apoptosis rate was significantly increased (P < 0.05), the protein expression levels of S100β, Rac1, p-Akt/Akt, p-NF-κB p65/NF-κB p65 in brain tissue were significantly increased (P < 0.05), and the expression of Arg-1 was significantly decreased (P < 0.05). Compared with model group, the above indicators were significantly improved in verbascoside group, electroacupuncture group, nifedipine group and verbascoside + electroacupuncture group (P < 0.05), among which the verbascoside + electroacupuncture group had a significantly better improvement effect than the verbascoside group and electroacupuncture group (P < 0.05). PMA could significantly reverse the improvement effect of verbascoside combined with electroacupuncture on IS rats (P < 0.05). Conclusion The combination of acteoside and electroacupuncture may alleviate neuroinflammation and brain tissue damage in IS rats by inhibiting Rac1/Akt/NF-κB pathway.

R285.5

河南省高等学校重点科研项目（25B310012）；南阳市基础与前沿技术研究专项计划项目（23JCQY2034）