延胡索总生物碱的急性毒性及其镇痛作用研究

Studies on Acute Toxicity and Analgesic Effects of Total Alkaloids of Corydalis Rhizoma

[目的]对延胡索总生物碱的小鼠急性毒性及镇痛作用进行评价。[方法]采用ICR小鼠单次给药毒性试验,观察延胡索总生物碱对小鼠的急性毒性反应和致死性,以Bliss法测定延胡索总生物碱对小鼠的半数致死量(median lethal dose,LD50)。采用醋酸扭体法考察延胡索总生物碱对外周的镇痛作用,ICR小鼠80只,雌雄各半,随机分成8组,分别为空白对照组、阳性对照组、延胡索乙素组、更高剂量组、高剂量组、中剂量组、低剂量组、更低剂量组,各组小鼠灌胃给药后1h,经腹腔注射0.6%冰醋酸0.2mL·20g-1,记录15min内小鼠的扭体次数,计算扭体次数抑制率;采用热板致痛试验考察延胡索总生物碱对中枢的镇痛作用,将筛选出的合格KM雌性小鼠80只随机分成8组,分组同上,各组于给药前重复测量痛阈3次,取平均值作为该小鼠给药前痛阈值,给药后30、90、180min各测定1次痛阈值。[结果]延胡索总生物碱灌胃给药对小鼠的LD50值为473.36mg·kg-1,95%置信区间为422.34~532.58mg·kg-1。与空白对照组比较,延胡索总生物碱各剂量组对小鼠扭体均具有显著的抑制作用,差异均具有统计学意义(P<0.01);除更低剂量组外,延胡索总生物碱各剂量组镇痛作用均优于延胡索乙素(P<0.01,P<0.05);除更低剂量组外,延胡索总生物碱各剂量组均能明显延长热板所致小鼠的痛阈值(P<0.01,P<0.05),各组痛阈值随浓度的增加呈上升趋势,且给药剂量达到120mg·kg-1后,痛阈值基本不再随浓度变化而变化。[结论]延胡索总生物碱具有明显的镇痛作用,在一定剂量范围内可安全使用。

[Objective]To investigate the acute toxicity and analgesic effects of total alkaloids of Corydalis Rhizoma on mice.[Methods]A single dose toxicity test was used to observe the acute toxicity and lethality of total alkaloids of Corydalis Rhizoma on ICR mice,and the median lethal dose(LD50)of total alkaloids of Corydalis Rhizoma was determined by Bliss method.The peripheral analgesic effect of total alkaloids of Corydalis Rhizoma was studied by acetic acid writhing method.Eighty ICR mice,half male and half female,were randomly divided into 8 groups,including blank control group,positive control group,tetrahydropalmatine(THP)group and higher dose group,high dose group,middle dose group,low dose group and lower dose group,mice in each group were intraperitoneally injected with 0.6%glacial acetic acid 0.2 mL·20 g-1 one hour after intragastric administration,and the number of writhings of mice within 15 mins was recorded,and the inhibition rate was calculated.The central analgesic effect of total alkaloids of Corydalis Rhizoma was investigated by hot plate pain test.Eighty selected female KM mice were randomly divided into 8 groups as above.Each group was repeatedly measured pain threshold for 3 times before administration,and the average value was taken as the pain threshold before administration,and the pain threshold was measured once every 30,90,and 180 minutes after administration.[Results]The LD50 of total alkaloids of Corydalis Rhizoma on mice was473.36 mg·kg-1,and the 95%confidence interval was 422.34~532.58 mg·kg-1.Compared with blank control group,the total alkaloids of Corydalis Rhizoma had a significant inhibitory effect on the writhing of mice,and the difference was statistically significant(P<0.01).Except for the lower dose group,the analgesic effect of the total alkaloids of Corydalis Rhizoma was better than that of THP(P<0.01,P<0.05).Except for the lower dose group,the total alkaloids of Corydalis Rhizoma of other dose could significantly prolong the pain threshold of mice induced by hot plate(P<0.01,P<0.05),the pain threshold of each group showed an increasing trend with the increase of concentration,and the dose threshold did not change with the concentration after the dose reached 120 mg·kg-1.[Conclusion]The total alkaloids of Corydalis Rhizoma can be used safely within a certain dose range and have obvious analgesic effects.