缬沙坦联合川芎嗪对血管性痴呆大鼠海马神经元损伤的保护作用

Protective Effect of Valsartan or/and Ligustrazine on Hippocampal Neuronal Loss in Rats with Vascular Dementia

目的研究缬沙坦联合川芎嗪对血管性痴呆(VD)大鼠学习记忆力的影响及海马神经元的保护。方法反复夹闭双侧颈总动脉并腹腔注射硝普钠复制VD大鼠模型;Morris水迷宫测大鼠空间学习记忆力;放射免疫法检测血浆精氨酸加压素(AVP)和血管紧张素Ⅱ(ANGⅡ)含量;化学比色法测定海马组织匀浆超氧化物歧化酶(SOD)、谷胱苷肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)含量;光镜观察海马神经元的损伤情况。结果与模型组比较,缬沙坦、川芎嗪治疗组大鼠逃避潜伏期缩短(P<0.05),在平台象限停留时间及跨越虚拟平台的次数增加(P<0.01);缬沙坦治疗组血浆AVP含量减少,川芎嗪治疗组血浆AVP含量增加(P<0.01);在各治疗组,ANGⅡ的含量增加(P<0.01),大鼠海马组织SOD、GSH-Px活性增加,MDA含量减少(P<0.05);光镜观察,各用药组大鼠海马神经元排列、数量、体积等结构损伤均减轻;上述指标除AVP外,均以联合用药组改善更为明显。结论缬沙坦联合川芎嗪对血管痴呆大鼠海马神经元的损伤具有较好保护作用。其原因可能与其抑制脑缺血再灌注所致肾素-血管紧张素系统(RAS)激活及自由基形成增加有关。

Objective To investigate the effect of Valsartan and Ligustrazine on hippocampal neuronal loss and the ability of learning and memory of rats with vascular dementia.Methods Vascular dementia was induced in rats by blocking bilateral carotid artery repeatedly and intraperitoneal injection of sodium nitroprusside.The vacuity learning and memory of the rats were measured with Morris water maze.The plasma AVP and ANGII were determined by radio-immunity methods.The activities of SOD,GSH-Px and MDA in hippocampal tissues were detected by chemistry colorimetry.The hippocampal neuronal loss was observe with light microscope.Results Both valsartan and ligustrazine shortened escape latency（P〈0.05）,and increased the numbers of rats crossing platform and the time spent in target quadrant（P0.01）.Valsartan decreased plasma AVP,whereas ligustrazine increased plasma AVP.Both valsartan and ligustrazine increased plasma ANGII（P〈0.01）,increased the activities of SOD and GSH-PX in hippocampal tissues,and decreased MDA activities in hippocampal tissues（P〈0.05）.The damages in structure,number and volume of hippocampal neuron cells were reduced by Valsartan and Ligustrazine.The combined use of Valsartan and Ligustrazine produced greater effects than either of the drugs alone in all of the indicators except for plasma AVP.Conclusion Valsartan or/and Ligustrazine have protective effect on hippocampal neuronal loss in rats with vascular dementia,possibly through inhibiting RAS activation and free radical formation induced by cerebral ischemia-reperfusion.