钩吻素子对孤立大鼠的抗焦虑作用及其机制

Discussion on the anxiolytic effect of koumine for the isolated rats and its mechanism

目的研究钩吻素子连续皮下给药对孤立大鼠抗焦虑样行为的影响,并探讨其作用机制。方法 Wistar大鼠单笼饲养18 d,第12天开始每天皮下注射钩吻素子0.5、1.5 mg/kg 1次,连续给药7 d。孤立饲养第17天(即给药第6天)进行高架十字迷宫试验,试验最后1 d(即给药第7天)进行自主活动试验和群居接触试验。行为学试验结束后,通过酶联免疫吸附测定(ELISA)检测动物血浆中促肾上腺皮质激素(ACTH)和皮质酮浓度,并测定海马中孕酮和别孕烯醇酮的含量。结果钩吻素子连续给药6 d能有效提高孤立大鼠在高架十字迷宫开臂区的活动情况,提示钩吻素子具有抗焦虑作用;钩吻素子连续给药7 d对大鼠自主活动无影响,但能提高配对孤立大鼠的接触次数和接触时间,进一步证明了钩吻素子的抗焦虑效应。与模型组比较,钩吻素子1.5 mg/kg治疗组能降低孤立大鼠血浆中的皮质酮水平(P<0.05),钩吻素子0.5、1.5 mg/kg治疗组均能提高大鼠海马中的别孕烯醇酮含量(P<0.01);而各组动物血浆中的ACTH浓度和海马中的孕酮含量则未见变化。结论钩吻素子连续给药能增加孤立大鼠的抗焦虑样行为,其抗焦虑作用可能与调节大鼠海马的别孕烯醇酮含量和抑制下丘脑-垂体-肾上腺轴异常活动有关。

Objective To study the anxiolytic effects of koumine administrated repeatedly on isolated rats and to explore its mechanism. Methods Each Wistar rat was housed in individual cage for 18 days, and at day 12, the rat was subcutaneously administrated of 0.5 or 1.5 mg/kg koumine once a day, lasting for 7 days. At the day 17 of individually housing （the sixth day of administration）, the elevated plus-maze was used to observe the anxiolytic-like behaviors of rats. And at the final day of individually housing （the seventh day of administration）, the behaviors of rats were mea- sured by the locomotor activity test and social interaction test subsequently. After the animal behavioral tests, the con- centrations of plasma adrenocorticotropic hormone （ACTH） and corticosterone, and the levels of progesterone and allo- pregnanolone in hippocampus of rats were measured by enzyme-linked immunosorbent assay （ELISA）. Results Repeat- ed administration of koumine for 6 days significantly increased activities of isolated rats in the open arms of elevated plus-maze, indicating the anxiolytic effect of koumine. After administration for 7 days, rats did not alter their locomo- tor activity, but the paired rats in 1,5 mg/kg koumine treatment group increased the contact number and contact time comparing with the model group, further demonstrating the effectiveness of koumine against anxiety. Comparing with the model group, 1.5 mg/kg koumine treatment reduced the concentration of plasma corticosteroue （P 〈 0.05）, and 0.5, 1.5 mg/kg of koumine treatment significantly increased the level of allopregnanolone in hippocampus of rats （P 〈 0.05）. The concentration of plasma ACTH and the level of progesterone in each group were not altered. Conclusion Repeated administration of koumine can increase the anxiolvtic-like behaviors of isolated rats. its anxiolvtic mechanism may be related to the mediation of allopregnanolone in hippocampus and the inhibition of abnormal activity of hypothalamic-pituitary-adrenal axis.