【摘要】 目的研究脑慢性低灌注（CCH）条件下海马神经胶质重构及加减薯蓣丸（MDP）干预,阐明CCH对海马神经胶质的影响及MDP作用机制。方法 40只SD大鼠按随机数字表法分为假手术组、模型组及药物组。采用改良的双血管阻断（2-VO）法制作CCH模型,药物组以加减薯蓣丸浓缩汤剂（湖北省中医院制剂室提供）进行灌胃45d(10g·kg^-1·d^-1),模型组和假手术组以生理盐水灌胃,剂量、疗程同药物组。疗程结束后采用水迷宫行为学实验对各组大鼠进行智能测定;取大鼠海马进行病理学观察及免疫组化测定Olig-2及GFAP表达,RT-PCR测定GAP-43mRNA表达。结果与模型组相比,药物组可明显降低定位航行逃避潜伏期（P<0.05）,增加跨越平台次数（P<0.01）;与假手术组相比,模型组海马组织辐射层、分子层、腔隙层纤维结构疏松,排列紊乱,星型胶质细胞明显增生;药物组海马辐射层,分子层及腔隙层纤维排列致密,星型胶质细胞增生明显减少,少突胶质细胞明显增生;药物组GFAP平均光密度值较模型组低,但较假手术组高,均达到极显著性差异（P<0.01）;药物组Olig-2平均光密度值较模型组高,较假手术组低,达到显著性差异（P<0.01,P<0.05）。假手术组、模型组、药物组GAP-43mRAN相互之间比较均达到统计学差异（P<0.01及P<0.05）。结论 CCH条件下海马神经胶质发生重构,表现为轴突丢失及髓鞘化程度低、胶质增生,可能是大鼠学习记忆受损的原因之一;加减薯蓣丸通过促进轴突的生成及髓鞘化,抑制星型胶质细胞增生,从而保持持神经纤维的正常有序联系,可能是其改善CCH状态下学习记忆能力的机制之一。更多还原

【Abstract】 Objective To clarify the impact of CCH on hippocampal glial and the mechanism of MDP,through studying on the hippocampal glial remodeling of rats subjected to chronic cerebral hypoperfusion（CCH）and interfered by the Modified Dioscorea Pills（MDP）.Methods 40 SD rats were randomly classified into sham operated group,model group and drug-treated group according to random number table.The modified 2-VO method was used to make CCH models.Rats in the drug-treated group were gavaged with MDP concentrated decoction(10 g·kg^-1·d^-1,supplied by Manufacturing Laboratory of Hubei Traditional Chinese Medicine Hospital)for 45 days,rats in the model group and sham operated group were gavaged with normal saline in same dosage and course.Adopted Morris Water Maze（MWM）test to determine the rats intelligence.The hippocampus tissue was harvested for pathology observation,immunohistochemistry check（Olig-2,GFAP）and RT-PCR（GAP-43 mRNA）.Results Compared to model group,rats in drug-treated group can significantly reduce the navigation latency（P<0.05）,increase the times of across the platform（P<0.01）.From HE staining,in the hippocampus of the model group,the fiber tissues of radiation layer,molecular layer and lacunar layer was looser and more disordered than those in sham operated group,more astrocytes hyperplasia can be seen.Whereas in the drug-treated group,they were dense,hyperplasia of astrocyte significantly reduced and oligodendrocyte proliferation was obvious.The average optical densities of GFAP in drug-treated group was lower than model group but higher than those in sham operated group,the results reach very significant levels（P<0.01）.The average optical densities of Olig-2 in drug-treated group was higher than model group but lower than those in sham operated group（0.012 6±0.00 038）,the comparisons reach significant levels（P<0.01,P<0.05）.The expressions of GAP-43 mRNA in sham operated group,model group and drug-treated group,the comparisons among them all reach significant level（P<0.01 or P<0.05）in statistics.Conclusion The remodeling of hippocampal glial tissue under CCH conditions is characterized by loss of axons,low degree of myelinization,more gliosis and so on,which may be one of the causes of impaired learning and memory in rats subjected to CCH.Through promoting the formation and myelination of axons,inhibiting astrocytes proliferation,MDP can maximum maintain the ordered connection of nerve fibers which underlie one of the mechanisms for MDP to improve learning and memory abilities.更多还原