目的 探究紫花前胡素调节趋化因子配体2（CCL2）-CC基序趋化因子受体2（CCR2）信号通路对脑缺血再灌注大鼠的神经保护作用。方法 将大鼠分为假手术组、模型组、紫花前胡素（10、25 mg/kg）组、紫花前胡素＋CCL2组、尼莫地平组，每组12只。除假手术组，其余大鼠均进行大脑中动脉闭塞/再灌注（MCAO/R）造模。紫花前胡素组大鼠分别ip 10、25 mg/kg紫花前胡素（溶于生理盐水）；紫花前胡素＋CCL2组大鼠ip 25 mg/kg紫花前胡素后，尾iv 1 µg CCL2重组蛋白；尼莫地平组大鼠ip 10.8 mg/g尼莫地平，其余组注射等量生理盐水，1次/d，给药7 d。给药后，测定大鼠神经学评分和脑水含量；TTC染色测定脑梗死体积；苏木素–伊红（HE）观察脑组织变化；免疫荧光染色检测脑组织紧密连接蛋白claudin-5表达；Western blotting检测脑组织CCL2、CCR2蛋白表达。结果 与模型组比较，紫花前胡素组大鼠神经学评分降低，脑水含量降低，脑梗死体积减少，脑组织水肿减轻，细胞形态改善，脑组织中claudin-5蛋白表达提高，CCL2、CCR2蛋白相对表达量降低（P＜0.05），且呈剂量相关性。与紫花前胡素组相比，紫花前胡素＋CCL2组大鼠脑组织损伤加重，紫花前胡素的神经保护作用被逆转（P＜0.05）。结论 紫花前胡素通过抑制CCL2-CCR2信号通路对脑缺血再灌注大鼠发挥神经保护作用。

Objective To explore the neuroprotective effects of decursin on cerebral ischemia-reperfusion rats by regulating the CCL2-CCR2) signaling pathway. Methods Rats were divided into the sham operation group, the model group, the decursin (10 and 25 mg/kg) group, decursin + CCL2 group, and the nimodipine group, with 12 rats in each group. Except for the sham operation group, middle cerebral artery occlusion/reperfusion (MCAO/R) modeling was performed in the remaining rats. The rats in the decursin group were respectively treated with ip at 10 and 25 mg/kg of decursin (dissolved in 0.9% normal saline). In the decursin + CCL2 group of rats, after ip at 25 mg/kg of decursin, tail iv was 1 µg of CCL2 recombinant protein. Rats in the nimodipine group received ip at a dose of 10.8 mg/g of nimodipine, while the other groups were injected with the same amount of normal saline once a day for 7 days. After administration, the neurological score and brain water content of rats were measured. TTC staining was used to measure the volume of cerebral infarction. Hematoxylin-eosin (HE) was used to observe changes in brain tissue. Immunofluorescence staining was performed to measure the tight junction protein claudin-5 in brain tissue. In addition, Western blotting was used to measure the CCL2 and CCR2 proteins in brain tissue. Results Compared with the model group, decursin groups showed decreased neurological scores, decreased brain water content, reduced cerebral infarction volume, reduced brain tissue edema, improved cell morphology, increased claudin-5 protein in brain tissue, and decreased CCL2 and CCR2 proteins expression (P < 0.05),with a dose-dependent correlation. Compared with the decursin group, the decursin + CCL2 group showed aggravated brain tissue damage, and the neuroprotective effect of decursin was reversed (P < 0.05). Conclusion Decursin exerts neuroprotective effects on cerebral ischemia-reperfusion rats by inhibiting CCL2-CCR2 signaling pathway.

R285.5

南充市科技计划项目（20YFZJ0025）