目的观察益气养阴活血法对糖尿病合并脑缺血大鼠空间学习记忆能力及脑源性神经营养因子(brainderived neurotrophie factor,BDNF)表达的影响,并运用工具药(BDNF的Trk受体抑制剂)证实BDNF通路在其中的作用。方法将大鼠分为假手术组、模型对照组(糖尿病合并脑缺血伴气阴两虚、瘀血阻络证)、益气养阴活血组、益气养阴活血+K252a组、益气活血组,每组20只,选用具有益气养阴活血作用的人参、川芎、玉竹、黄精组合,运用免疫组织化学法和Morris水迷宫实验观察益气养阴活血药对糖尿病合并脑缺血模型大鼠空间学习记忆的作用及对BDNF表达的影响。结果与模型对照组比较,益气养阴活血药物和益气活血药物均可以明显增加糖尿病合并脑缺血大鼠海马齿状回BDNF的表达(P〈0.01),益气养阴活血药物显著缩短模型大鼠找到水下平台的潜伏期(P〈0.01),益气养阴活血药物和益气活血药物均显著延长大鼠在原水下平台的停留时间(P〈0.05,或P〈0.01),其中益气养阴活血药物效果优于益气活血药物(P〈0.05)。侧脑室注射K252a可以阻断益气养阴活血药物促进模型大鼠的空间记忆能力的恢复(P〈0.01)。结论益气养阴活血药物可能通过促进模型大鼠海马齿状回BDNF的表达而改善空间记忆功能。
Objective To observe the effects of qi-supplementing, yin-nourishing, and blood circulation- activating (QYB) prescription on the expression of brain-derived neurotrophic factor (BDNF) in the hippo- campus and spatial learning and memory ability in diabetic rats with cerebral ischemia and to verify the role of BDNF pathway in spatial learning and memory using the inhibitor of the Trk receptor of BDNF (K252a). Methods One hundred rats were equally divided into sham operation group, model control group (with diabetes associated with cerebral ischemia plus syndromes of deficiency of both qi and yin and blood stasis obstructing the collaterals), QYB group, QYB+K252a group, and qi-supplementing and blood circulation-activating (QB) group. The effects of QYB prescription, which was composed of Panax ginseng, Rhizoma Ligustici Chuanxiong, Polygonatum odoratum, and Polygonatum sibiricum, on the spatial learning and memory ability and BDNF expression in diabetic rats with cerebral ischemia were observed by immu- nohistochemistry and Morris water maze test. Results Compared with the model control group, the QYB group and QB group had significantly higher BDNF expression in the fascia dentata of the hippocampus (P〈0.01),V1SI QYB group had significantly shorter escape latency period, the time taken to reach the submerged, in- ble platform (P~0.01), and the QYB group and QB group had significantly prolonged time spent in the platform area (P%0.05 or P%0.01). The QYB group showed a significantly better performance than the QB group (P%0.05). K252a injected into the lateral ventricle could inhibit the positive effects of QYB prescription on the spatial memory ability of the rat model (P%0.01). Conclusion QYB prescription can promote the BDNF ex- pression in the fascia dentata of the hippocampus in diabetic rats with cerebral ischemia, thus improving their spa- tial memory ability.