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[摘要]
目的 考察丹酚酸B鼻腔给药后在大鼠海马组织的分布及鼻腔给药对脑缺血损伤大鼠学习记忆能力的影响,并初步探讨其作用机制。方法 采用高效液相色谱法检测鼻腔给药后不同时间大鼠海马组织丹酚酸B的浓度;采用四动脉结扎法复制大鼠脑缺血模型,随机分为假手术组、模型组、丹酚酸B鼻腔给药组,于脑缺血后1周开始给药,每天1次,连续3周。采用Morris水迷宫方法,考察丹酚酸B鼻腔给药对脑缺血损伤大鼠空间学习记忆能力的影响。采用甲酚紫(尼氏)染色法,考察丹酚酸B鼻腔给药对脑缺血损伤大鼠海马区形态学特征的影响。采用BrdU标记及免疫组织化学法考察丹酚酸B鼻腔给药对脑缺血损伤大鼠海马区新生神经细胞存活的影响。结果 脑内药物浓度测定结果显示丹酚酸B鼻腔给药可在海马组织有一定分布,其峰浓度(Cmax)为(2.47±0.55)μg/g,曲线下面积(AUC)为(336.4±73.0)μg·min/g;Morris水迷宫实验结果显示丹酚酸B鼻腔给药可以降低脑缺血损伤大鼠的平均逃避潜伏期,延长脑缺血损伤大鼠在原平台象限停留时间(P<0.05),增加脑缺血损伤大鼠跨越原平台次数(P<0.05)。形态学结果显示模型组大鼠海马CA1区细胞层数减少,锥体细胞数目明显减少,且排列不规则;与模型组比较,丹酚酸B鼻腔给药组海马形态结构清晰,神经细胞排列较规则,神经元数目明显增多;BrdU标记结果显示脑缺血损伤稳定后假手术组和模型组BrdU阳性细胞数目无明显变化,但丹酚酸B鼻腔给药组BrdU阳性细胞数目显著增多(P<0.01)。结论 丹酚酸B鼻腔给药可在海马组织有一定的药物分布,可以明显改善脑缺血损伤导致的学习记忆能力,这种作用可能与直接促进海马神经干细胞增殖有关。
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[Abstract]
Objective To study the concentration of salvianolic acid B (Sal B) in rat hippocampus after intranasal administration, and to inveategate the improvement on cognitive dysfunction of rats with cerebral ischemic treated by intranasal administration of Sal B and its mechnisms. Methods HPLC method was employed to check the distribution of Sal B in hippocampus by intranasal administration. Sal B was intranasal administered after one week of cerebral ischemia. The effect of Sal B by intranasal administration on cognitive dysfuctiopn was checked using Morris water maze. The effect of Sal B by intranasal administration on the hippocampus morphological characteristics was studied using Cresyl violet (Nissl) staining. BrdU injection and immunohistochemical staining were used to test the effect of Sal B on the neurogensis in hippocampus of cerebral ischemic rats. Results After intranasal administration of Sal B, the Cmax of Sal B was (2.47 ±0.55) μg/g, and the AUC of Sal B was (336.4 ±73.0) μg·min/g. Morris water maze test results showed that Sal B by intranasal administration could reduce the average escape latency of cerebral ischemic rats, increase the time in the former platform quadrant and the time of rats across the platform. Compared with the Sham group, the hippocampal CA1 cell layers were reduced and the pyramidal cells showed an irregular arrangement in the model group. Compared with model group, hippocampal morphology was clear, nerve cells arranged in regular, and the number of neurons increased significantly in groups of Sal B by intranasal administration. Immunohistochemistry results showed that the groups of Sal B by intranasal administration could increase the BrdU-positive cell number in hippocampus. Conclusion Intranasal administration of SalB can significantly improve the distribution in the hippocampus. Intranasal administration of Sal B could improve the cognitive dysfuction, and this effect maybe related to the directive effect of Sal B on promoting neurogenesis after cerebral ischemic.
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