脑力苏胶囊改善血管性痴呆大鼠智能障碍的实验研究

【作者】 岳仁宋；

【导师】 张发荣；

【作者基本信息】 成都中医药大学 ， 中医内科学， 2004， 博士

【副题名】脑力苏胶囊对大鼠海马组织形态学、NOS、AchE、ACP、CCO及NGFmRNA的影响

【摘要】 目的 采用水迷宫、酶组化、免疫组化、原位杂交等方法，通过脑力苏胶囊对血管性痴呆(Vascular Dementia VaD)大鼠学习记忆及海马组织形态学，一氧化氮合酶(nitricoxidesyn thase NOS)、酸性磷酸酶(Acid phosphatase ACP)、乙酰胆碱脂酶(acety]cholinesterase AchE)、细胞色素氧化酶(Cytochrome Oxidase CCO)酶活性，神经型一氧化氮合酶(nNOS)阳性细胞及神经生长因子(Nerve growth factor NGF)转录影响的研究，探讨脑力苏胶囊对血管性痴呆大鼠智能障碍的改善效果及作用机理。方法 根据Olsson方法，采用永久性阻断双侧颈总动脉复制VaD大鼠模型，随机分为模型组、喜德镇组、大剂量脑力苏胶囊组、中剂量脑力苏胶囊组、小剂量脑力苏胶囊组，并加假手术组(每组10只)，共用药21d。于造模前、后及用药后用水迷宫检测学习、记忆情况；借助光镜、HE染色、酶组化、免疫组化、原位杂交等方法对海马组织形态学、ACP、Ache、CCO、NOS酶活性、nNOS阳性细胞及NGFmRNA进行观测。结果 大剂量脑力苏胶囊、喜德镇治疗后大鼠学习记忆(智能)明显改善(P＜0.05)，海马CAl区锥体细胞丢失明显减少，ACP、NOS酶活性降低，CCO、AchE酶活性增加，nNOS阳性神经元下降，NGFmRNA转录增强。结论 大剂量脑力苏胶囊能改善VaD大鼠学习记忆能力，使CCO、AchE酶活性上升，ACP、Ache、NOS酶活性下降，说明了脑力苏胶囊可以改善脑缺血状态，保护脑缺血性损伤，从而对缺血引起的VaD具有益智、增智作用；此外，脑力苏胶囊还通过促进海马NGFR的转录，抑制nNOS活性，调节中枢神经系统兴奋性与抑制性的平衡，提高神经细胞对缺氧的耐受性，减少神经元的丢失，改善学习记忆能力。大剂量脑力苏胶囊的作用与喜德镇相近。更多还原

【Abstract】 Objective: Using Water maze , zymohistochemical method, immunohistochemical method as well as in situ hybridization, to discuss the effect and action mechanism of Nao Li Su (NLS) Capsule when treating the intelligent disorder of vascular dementia rats, through the stucy of influences of NLS Capsule on learning and memory abilities of vascular dementia rats, on hippocampal histomorphology , on the activity of nitricoxide synthase(NOS), Acid phosphatase (ACP), acetylchlinesterase (AchE) and Cytochrome Oxidase (CCO), on the transcription of nNOS positive cells and Never growth factor(NGF). Method: According to Olsson’ s method, we replicated Vad rats model by blocking bilateral common carotid artery permanently and randomly classified into six groups, namely, model group, control group, NLS capsule high group, NLS capsule middle group, NLS capsule low dos group and pseudo-operation group(ten each group). The treatment lasted for twenty-one days. Water maze was used to test the learning and memory abilities of these Vod rats before and after making model and after treatment; We observed hippocampal histomorphology, the activity of ACP, CCO and NOS nNOS positive cells as well as NGFmRNA in virtue of light microscope, HE staining, zymohistochemical, immunohistochemical, genetic expression etc.Result: The learning and memory abilities of rats obviously improved (P<0. 05), the lose of hippocampal CA1 area pyramidal cells decreased apparantly; ACP, NOS activity andnNOS positive neuron decreased ; CCO, AchE activity increase ; NGFmRNA transcription is enhanced after trentment of high dosage NLS capsule and Dihydergotoxine. Conclusion: High dosage NLS capsule can improve the learning and memory ability ,increase CCO, AchE activity and decrease ACP, NOS activity . It indicated that NLS capsule can improve the cerebral ischemic state , protecte cerebral ischemic injury , accordingly to promote intelligence. Furthermore, NLS Capsule can inhibit the activity of nNOS via promoting the transcription of hippocampal NGFR, can regulate the balance between excitability and inhibitility of central nerves system, can increase the tolerance of neurocyte for hypoxia, can decline the lose of neuron and improve learning and memory abilities . And the effect of High dosage NLS Capsule is similar with that of Dihydergotoxine.更多还原