均值化邓氏关联度计算法对不同给药剂量的瓜蒌滴丸谱效关系的影响

目的探讨均值化邓氏关联度计算方法对瓜蒌滴丸抗凝血作用谱效关系的影响,为后续采用灰关联方法进行谱效关系研究提供参考和借鉴。方法采用高效液相色谱法(HPLC)建立10批瓜蒌滴丸的HPLC指纹图谱。选取320只小鼠,随机分为32组(1个空白组、1个阳性对照组、30个瓜蒌滴丸组),每组10只小鼠。空白组给予纯水,阳性对照组给予复方丹参滴丸(给药剂量为:0. 123 g/kg),瓜蒌滴丸组给予10批瓜蒌滴丸,每批3个剂量(0. 475 g/kg、4. 75 g/kg、9. 50 g/kg)共30组,每天灌胃1次,给药7 d。7日后摘眼球取血测定小鼠活化部分凝血活酶时间(APTT)值。采用邓氏关联度法等7种不同灰关联度计算方法研究瓜蒌滴丸HPLC指纹图谱与3种给药剂量的小鼠APTT的谱效关系,并对邓氏关联度计算方法进行改进,建立均值化邓氏关联度计算方法,同时观察其对瓜蒌滴丸抗凝血作用谱效关系的影响。结果邓氏关联度计算方法所得谱效关系与瓜蒌滴丸已知成分药效相符,但不能体现不同给药剂量间的量效关系;绝对关联度等其他6种方法无法准确反映谱效关系;均值化邓氏关联度计算方法所得谱效关系前10位为:19(腺苷)> 9> 7> 13(鸟苷)> 2(尿嘧啶)> 1> 5(次黄嘌呤)> 4> 29> 6,且呈量效关系,这与瓜蒌滴丸已知成分药效相符。结论邓氏关联度等7种不同灰关联度法用于瓜蒌滴丸谱效关系分析还有待进一步改进和完善。均值化邓氏关联度计算方法可用于不同给药剂量瓜蒌滴丸的谱效关系分析。

The mean value calculation method of Deng's correlation degree on spectrum effect relationship of different doses of Fructus Trichosanthis dropping pills

Objective To study the mean value calculation method of Deng''s correlation degree on the spectrum effect relationship of anticoagulant effect of Fructus Trichosanthis dropping pills, so as to provide reference for future study of spectrum effect relationship by grey relational correlation method. Methods HPLC fingerprint of 10 batches of Fructus Trichosanthis dropping pills was established by HPLC. A total of 320 qualified rats were divided randomly into 32 groups with 10 rats in each group, half male and half female, then the experimental groups were respectively given 10 batches Gualou dropping pills at doses of 9.50 g/kg, 4.75 g/kg, 0.475 g/kg by gavage one time a day for seven days. The blank group was given pure water by gavage and the positive control group was given Compound Danshen Drop Pills at doses of 0.123 g/kg. APTT (activated partial thromboplastin time) in mice was determined seven days later by taking blood from eyeballs. The spectrum effect relationship between HPLC fingerprints of Fructus Trichosanthis dropping pills and three doses of mouse APTT was studied using seven different grey relational degree calculation methods. The calculation method of Deng''s correlation degree was improved, and the method of calculating the mean value of Deng''s correlation degree was established. Meanwhile, the effect of Trichosanthis drop pills on APTT spectrum effect relationship was observed. Results The spectrum effect relationship obtained by means of the mean value calculation method of Deng''s correlation degree was consistent with the efficacy of the known ingredient of Fructus Trichosanthis dropping pills, and it can reflect the dose-effect relationship between different dosages. The top ten spectral effect relations obtained by the mean value calculation method of Deng''s correlation degree are 19 (adenosine) > 9 > 7 > 13 (guanosine) > 2 (uracil) > 1 > 5(hypoxanthine) > 4 > 29 > 6, presenting a dose-effect relationship. However, other methods such as absolute correlation degree and so on, can not accurately reflect the spectrum effect relationship. Conclusions Seven different grey correlation methods, such as Deng''s correlation and so on, need further improvement if applied to the analysis of spectrum effect relationship. However, the mean value calculation method of Deng''s correlation degree can be applied to the analysis of spectrum effect relationship of different dosages of Fructus Trichosanthis dropping pills.