梓醇对脑缺血急性期及亚急性期的神经保护作用及作用机制

Neuronal Protective Effect and Mechanism of Catalpol on Acute and Subacute Phase after Cerebral Ischemia

目的：探讨梓醇对永久性脑缺血模型急性期脑组织梗死体积、含水量及亚急性期炎性反应的影响。方法：采用化学刺激法建立局灶性脑缺血（MCAT）模型，检测急性期（24 h）神经行为学症状、脑梗死面积和脑含水量；线栓法制作永久性大鼠脑缺血（pMCAO）模型，酶联免疫吸附法（ELISA）测定缺血侧脑组织白细胞介素-6（IL-6）、白细胞介素-10（IL-10）和核转录因子Bp65（NF-κBp65）的含量。结果：大鼠MCAT后24 h，梓醇15-60 mg＆#183;kg-1剂量组可以显著改善模型动物神经症状损伤（P〈0.01或P〈0.001），梓醇15 mg＆#183;kg-1组可显著降低模型动物梗塞区面积（P〈0.05），30 mg＆#183;kg-1组和60 mg＆#183;kg-1组可显著降低脑水肿（P〈0.05）；大鼠pMCAO术后7天开始，梓醇30 mg＆#183;kg-1组或60 mg＆#183;kg-1组开始改善模型动物神经症状损伤；术后14天，与假手术组比较，缺血侧脑组织IL-10和核转录因子NF-κBp65的含量变化与模型组已经不明显，IL-6水平显著降低（P〈0.05），梓醇15 mg＆#183;kg-1灌胃14天可以降低模型动物缺血侧脑组织NF-κBp65含量（P〈0.05）。结论：梓醇能改善局灶性脑缺血模型动物急性期及亚急性期神经症状损伤，缩小梗死灶，减轻脑部水肿，其作用可能与抑制脑缺血引起的炎症损伤无关。

This study was aimed to explore the effect of Catalpol on the cerebral infarction size in acute phase, water content and inflammatory reaction of early recovery after permanent middle cerebral artery occlusion （pM-CAO）. Adult male Sprague-dawley rats were subjected to chemical method to establish MCAT model. The detec-tion was made on neurobehavioral symptoms, cerebral infarction volume and water content at 24 h after surgery. The content of intedeukin-6 （IL-6）, intedeukin-10 （IL-10） and nuclear factor kappa Bp65 （NF-κBp65） were de-tected after pMCAO with enzyme-linked immunosorbent assay （ELISA）. The results showed that 24 h after MCAT, Catalpol 15-60 mg＆#183;kg-1 can significantly improve the neurobehavioral symptoms （P 〈 0.01, or P 〈0.001）. The Catalpol 15 mg＆#183;kg-1 can significantly reduce cerebral infarction volume （P 〈 0.05）. The Catalpol 30-60 mg＆#183;kg-1 can significantly reduce water content （P 〈 0.05）. Catalpol 30-60 mg＆#183;kg-1 can significantly improve neurobehav-ioral symptoms from the 7th day after pMCAO. On the 14th after pMCAO, the content of IL-10 and NF-κBp65 of ischemia brain had no difference compared with sham-operated group. The IL-6 level of ischemia brain was obvi-ously reduced than the sham-operated group（P 〈 0.05）. The intragastric administration of Catalpol 15 mg＆#183;kg-1 for 14 days can reduce the content of NF-κBp65 in the ischemia brain of model rats （P 〈 0.05）. It was concluded that Catalpol can improve neurobehavioral symptoms of acute and subacute phase after cerebral ischemia, reduce infarcts and water content. These effects may not be related with its inhibition of inflammatory derived from cere-bral ischemia.