艾灸督脉组穴对血管性痴呆大鼠学习记忆能力和RAGE、LRP-1表达的影响

目的观察艾灸督脉组穴对血管性痴呆(vascular dementia,VD)大鼠脑微血管内皮细胞(brain microvascular endothelial cells,BMECs)晚期糖基化终产物受体(receptor for advanced glycation end products,RAGE)和低密度脂蛋白受体相关蛋白-1(LDL-receptor related protein-1,LRP-1)表达的影响,探讨艾灸督脉组穴治疗VD的作用机制。方法采用Morris水迷宫筛选后,将SD大鼠随机分为正常组、模型组、艾灸组,每组12只。采用颈总动脉结扎反复缺血再灌注法复制模型,艾灸组取“百会”“大椎”“风府”温和灸30 min,每日1次,7次为1个疗程,共治疗4个疗程。采用Morris水迷宫法对大鼠进行行为学检测,采用免疫组织化学法检测皮质和海马组织中RAGE和LRP-1表达水平,并分析行为学检测结果与RAGE和LRP-1之间的相关性。结果各时间点模型组逃避潜伏期均较正常组明显延长(P<0.05),艾灸组逃避潜伏期均较模型组明显缩短(P<0.05);模型组大鼠穿越平台次数明显少于正常组(P<0.05),艾灸组大鼠穿越平台次数明显多于模型组(P<0.05)。与正常组比较,模型组大鼠海马和皮质中RAGE表达增多,LRP-1表达减少,差异均有统计学意义(P<0.05);与模型组比较,艾灸组大鼠海马和皮质中RAGE表达减少、LRP-1表达增多,差异均有统计学意义(P<0.05)。大鼠穿越平台次数与海马和皮质内RAGE存在显著负相关关系,与海马和皮质内LRP-1存在显著正相关关系。结论艾灸督脉组穴可明显改善VD大鼠的学习记忆能力,其机制可能与下调大鼠BMECs的RAGE表达和上调LRP-1表达有关。

Effect of Moxibustion at Paired Acupoints of the Governor Vessel on Learning-Memory Ability and Expression of Receptor for Advanced Glycation End Products and LDL Receptor-Related Protein-1 in Rats with Vascular Dementia

Objective To investigate the effect of moxibustion at paired acupoints of the governor vessel on the expression of receptor for advanced glycation end products (RAGE) and LDL receptor-related protein-1 (LRP-1) in brain microvascular endothelial cells (BMECs) in rats with vascular dementia, as well as the mechanism of moxibustion at paired acupoints of the governor vessel in the treatment of vascular dementia. Methods After screening by the Morris water maze test, Sprague-Dawley rats were randomly divided into normal group, model group, and moxibustion group, with 12 rats in each group. A model of vascular dementia was established by common carotid artery ligation to induce recurrent ischemia/reperfusion. The rats in the moxibustion group were given mild-warm moxibustion at Baihui, Dazhui, and Fengfu acupoints for 30 minutes per day; each course of treatment was 7 days, and the rats were treated for 4 courses. The Morris water maze test was used for behavioral analysis, and immunohistochemistry was used to measure the expression of RAGE and LRP-1 in the cortex and the hippocampus. The correlation between behavioral test results and RAGE/LRP-1 was also analyzed. Results At each time point, the model group had a significantly longer escape latency than the normal group (P<0.05), and the moxibustion group had a significantly shorter escape latency than the model group (P<0.05); the model group had a significantly lower number of platform crossings than the normal group (P<0.05), and the moxibustion group had a significantly higher number of platform crossings than the model group (P<0.05). Compared with the normal group, the model group had a significant increase in the expression of RAGE and a significant reduction in the expression of LRP-1 in the cortex and the hippocampus (P<0.05); compared with the model group, the moxibustion group had a significant reduction in the expression of RAGE and a significant increase in the expression of LRP-1 in the cortex and the hippocampus (P<0.05). The number of platform crossings was negatively correlated with RAGE in the cortex and the hippocampus and was positively correlated with LRP-1 in the cortex and the hippocampus. Conclusion Moxibustion at paired acupoints of the governor vessel can significantly improve learning-memory ability in rats with vascular dementia, possibly by downregulating the expression of RAGE and upregulating the expression of LRP-1 in BMECs.