病/证状态对附子急性毒性与药效影响探析

Study on Acute Toxicity and Effect of Aconite Roots Based on Disease/Syndrome

目的:初步观察病/证状态对附子毒性及药效的影响,探讨病/证-毒-效的相关性。方法:小鼠接受风寒刺激模拟寒证,冰醋酸腹腔注射复制小鼠疼痛模型;比较生附子对正常小鼠和风寒刺激小鼠的LD50及镇痛作用的ED50,计算治疗指数(Therapeutic Index,TI)。大鼠接受风寒刺激模拟寒证,Ⅱ型胶原(CⅡ)与弗氏完全佐剂(CFA)皮内注射建立类风湿性关节炎(Rheumatoid Arthritis,RA)大鼠模型;描记Ⅱ导联心电图比较黑顺片对正常组、RA模型组、RA+风寒刺激组大鼠心脏毒性的TD50及关节肿胀度。结果:风寒刺激后,动物出现与中医寒证相似的表现。与正常组比较,生附子粉对风寒刺激组小鼠的LD50升高,而镇痛作用的ED50降低,治疗指数明显升高;与正常组比较,黑顺片对RA模型组及RA+风寒刺激组大鼠心脏毒性的TD50升高,对RA+风寒刺激组大鼠关节肿胀的改善作用优于单纯RA模型组。结论:在病/证状态下,附子的毒性呈降低趋势,药效呈上升趋势,提示证候-毒性-药效之间存在一定的相关性。

This study was aimed to observe influence of disease/syndrome on the toxicity and effect of aconite roots, in order to reveal relationship among disease/syndrome, toxicity and effect. The mice model of cold syn-drome was establish by wind-cold stimulation. The pain model was established by intraperitioneal injection of glacial acetic acid. Then, LD50 and ED50 of analgesic effect were compared, as well as the therapeutic index （TI） of crude aconite roots. The rat model of cold syndrome was also established by wind-cold stimulation. And the rheumatoid arthritis （RA） model was established by intracutaneous injection of CII and CFA. TD50 of cardiac toxic-ity and arthroncus degree of prepared aconite roots were compared among the normal rats, RA rats, RA with wind-cold stimulation rats according to the recording of lead II ECG. The results showed that after wind-cold stimulation, mice and rats appeared with symptoms which were similar to Chinese medicine cold syndrome. Com-pared with normal mice, LD50 and TI increased, but ED50 decreased in the group of wind-cold stimulation after using powders of crude aconite roots. Compared with normal rats, TD50 of cardiac toxicity and arthroncus degree in-creased in groups of RA and RA with wind-cold stimulation after using prepared aconite roots. It was concluded that in the case of disease/syndrome state, the toxicity of aconite roots decreased, but its effect increased. It sug-gested that there is a significant correlation among disease/syndrome, toxicity and effect.