Zhu Kun-Jie, Sun Jian-Ning, Ma Chang-Hua, Geng Yao
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102 China.
Zhongguo Zhong Yao Za Zhi. 2007 May;32(10):949-53.
To probe the mechanism of EEG activation and Xingnao Kaiqiao, evaluate the actions of cinnabaris and realgar in Xingnao Kaiqiao of Angong Niuhuang pill, guess the significance of cinnabaris and realgar in specific indication treatment of Angong Niuhuang pill, and provide experimental bases for the rationality of Angong Niuhuang pill building-up.
Seventy SD rats were divided into seven groups: the control, the model, the Angong Niuhuang pill (0.4 g x kg(-1)), the Angong Niuhuang pill without cinnabaris and realgar (0.32 g x kg(-1)) , the cinnabaris and realgar (0.08 g x kg(-1)), the realgar (0.04 g x kg(-1)), and the cinnabaris (0.04 g x kg(-1)). Rats in the control and model groups were given distilled water. After three days of administration, the brain damage model was made by Lipopolysaccharides (LPS) injection through caudal vein and the catecholamine (CA) and its metabolites levels in cerebral cortex, included noradrenaline (NE), adrenaline (E), 3-methocy-4-hydroxyphenylglycol (MHPG), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), Homovanlic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), were determined by high-performance liquid chromatography with electrochemical detector (HPLC-ECD). Influences of Angong Niuhuang pill, Angong Niuhuang pill without cinnabaris and realgar, cinnabaris and realgar on monoamine transmitters were observed in brain damage rats caused by LPS.
LPS could raise NE, 5-HT, 5-HIAA levels and reduce E, DOPAC levels, but had no influence on HVA, DA, MHPG levels. Angong Niuhuang pill had the trend of raising E, DOPAC levels and reducing NE level, and could reduce 5-HIAA level obviously comparing with models. But Angong Niuhuang pill without cinnabaris and realgar was different, NE level was significantly higher compared to models and Angong Niuhuang pill, DA level was also significantly higher compared to all groups. Cinnabaris and realgar had the same action trends with Angong Niuhuang pill, and separate realgar could obviously reduce 5-HT.
Influence on CA and its metabolites levels in cerebral cortex may be one of the mechanisms of Angong Niuhuang pill's EEG activation, and cinnabaris and realgar have the same action on CA levels in cerebral cortex. The results of the present work allow us to put forward the hypothesis that cinnabaris and realgar are most likely one of the important material basis in Xingnao Kaiqiao of Angong Niuhuang pill.
探讨脑电图激活及醒脑开窍机制，评价安宫牛黄丸中朱砂和雄黄在醒脑开窍方面的作用，推测朱砂和雄黄在安宫牛黄丸特定适应证治疗中的意义，为安宫牛黄丸组方合理性提供实验依据。
将70只SD大鼠分为7组：对照组、模型组、安宫牛黄丸组（0.4 g·kg⁻¹）、去朱砂雄黄安宫牛黄丸组（0.32 g·kg⁻¹）、朱砂雄黄组（0.08 g·kg⁻¹）、雄黄组（0.04 g·kg⁻¹）、朱砂组（0.04 g·kg⁻¹）。对照组和模型组大鼠给予蒸馏水。给药3天后，经尾静脉注射脂多糖（LPS）制作脑损伤模型，采用高效液相色谱-电化学检测器（HPLC-ECD）测定大脑皮质中儿茶酚胺（CA）及其代谢产物水平，包括去甲肾上腺素（NE）、肾上腺素（E）、3-甲氧基-4-羟基苯乙二醇（MHPG）、5-羟色胺（5-HT）、5-羟吲哚乙酸（5-HIAA）、多巴胺（DA）、高香草酸（HVA）、3,4-二羟基苯乙酸（DOPAC）。观察安宫牛黄丸、去朱砂雄黄安宫牛黄丸、朱砂雄黄对LPS所致脑损伤大鼠单胺类递质的影响。
LPS可使NE、5-HT、5-HIAA水平升高，E、DOPAC水平降低，但对HVA、DA、MHPG水平无影响。安宫牛黄丸有使E、DOPAC水平升高及NE水平降低的趋势，与模型组比较可明显降低5-HIAA水平。但去朱砂雄黄安宫牛黄丸不同，与模型组和安宫牛黄丸组比较NE水平显著升高，与各给药组比较DA水平也显著升高。朱砂雄黄与安宫牛黄丸作用趋势相同，单独雄黄可明显降低5-HT。
对大脑皮质CA及其代谢产物水平的影响可能是安宫牛黄丸脑电图激活的机制之一，朱砂和雄黄对大脑皮质CA水平有相同作用。本研究结果使我们提出如下假说：朱砂和雄黄很可能是安宫牛黄丸醒脑开窍的重要物质基础之一。
