Hippocampal CA1 pyramidal cells and neurotrophic factors in a rat model of vascular dementia following Xiongma drop pill versus Ginkgo leaf tablets

摘要

BACKGROUND: Previous studies have demonstrated the neuroprotective effects of Xiongma droppill (XMDP) in a mouse model of vascular dementia. Neurotrophic factors play an important role inrepair and regeneration of injured neurons.OBJECTIVE: To compare the effects of XMDP and Ginkgo leaf tablets on the appearance andnumber of hippocampal CA1 pyramidal neurons, as well as neurotrophic factor content in braintissues, during vascular dementia formation to explore the neuroprotective mechanisms of XMDP.DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at theLaboratory of Pharmacology, College of Pharmacy, Harbin University of Commerce between April2007 and December 2008.MATERIALS: XMDP was prepared by the College of Pharmacy, Harbin University of Commerce,with each 40 mg pill containing ferulic acid (≥ 0.149 mg) and gastrodin (≥ 0.171 mg). Ginkgo leaftablets were purchased from Taiyuan Qianyuan Pharmacy, China.METHODS: Healthy, adult, male, Wistar rats were randomly assigned to 6 groups: sham-operation,model, XMDP (high-, middle-, and low- dose), and Ginkgo leaf tablets. The 6 groups weresubdivided into two subgroups according to administration days, i.e., 30 and 60 days, with 8 animalsin each subgroup. Rats in the model, XMDP, and Ginkgo leaf tablets groups were subjected topermanent bilateral ligation of the common carotid artery to establish a vascular dementia model. At8 days after model establishment, all groups received intragastric administration once daily of thefollowing: 10 mL/kg normal saline in the sham-operation and model groups; 0.4, 0.2, and 0.1 g/kgXMDP in the high-, middle-, and low-dose XMDP groups, respectively; and 50 mg/kg Ginkgo leaftablets in the Ginkgo leaf tablets group.MAIN OUTCOME MEASURES: Hematoxylin-eosin staining was used to observe appearance andto quantify the number of hippocampal CA1 pyramidal neurons. Brain-derived neurotrophic factorand nerve growth factor concentrations in brain tissues were detected by enzyme-linkedimmunosorbent assay.RESULTS: Following model establishment, hippocampal CA1 neurons exhibited pathologicalchanges. Compared with the sham-operation group, the number of pyramidal neurons significantlydecreased (P < 0.05 or P < 0.01 ), and neurotrophic factor concentration increased in the model rats(P < 0.05 or P < 0.01). XMDP attenuated neuronal injury in a dose-dependent manner: the numberof pyramidal neurons and neurotrophic factor concentrations were significantly increased comparedwith the model group (P< 0.05 or P< 0.01). High- and middle-dose XMDP resulted in equivalenteffects to Ginkgo leaf tablets. In addition, neurotrophic factor concentrations in all XMDP groups,after 60 days of administration, were remarkably greater than corresponding concentrations at 30days (P < 0.05 or P < 0.01).CONCLUSION: Hippocampal CA1 pyramidal cells exhibited pathological injury followingestablishment of the vascular dementia model. Middle- and high-dose XMDP increased neurotrophicfactor expression in the brain of vascular dementia rats, which suggested neuroprotection equivalentto Ginkgo leaf tablets.