刘锦林 潘彦舒 李海燕 程晓娜 王东辉 牟天龙 刘元

摘要：目的 观察黄芩苷对脑缺血雌性大鼠血清孕酮及其相关激素水平的影响，探讨其是否通过调控孕酮水平发挥对脑缺血大鼠神经功能的保护作用。方法 应用阴道涂片方法选取成年动情期雌性大鼠，随机分为正常组、正常+黄芩苷组和造模组。造模组制作左侧大脑半球永久性大脑中动脉栓塞模型，成模后随机分为模型组、黄芩苷组、孕酮组和孕酮抑制剂组。正常+黄芩苷组和黄芩苷组腹腔注射黄芩苷溶液，正常组和模型组腹腔注射等量生理盐水，孕酮组给予黄体酮注射液肌注，孕酮抑制剂组给予黄芩苷溶液腹腔注射和米非司酮溶液灌胃。分别于造模后不同时间点抓力测定仪检测各组大鼠前肢抓力，并进行神经功能行为评分；ELISA检测血清孕酮及其相关激素的水平。结果 与正常组比较，造模各组大鼠神经功能发生损伤，各时间点神经功能行为评分均极显著升高（P<0.001），各时间点前肢抓力均极显著降低（P<0.001）。治疗5 d，黄芩苷组显示出对神经功能改善的趋势（P>0.05），并可显著提高前肢抓力（P<0.01）；治疗10 d，黄芩苷组显著改善神经功能行为评分（P<0.05），并极显著提高大鼠前肢抓力大小（P<0.001）；与黄芩苷组比较，孕酮抑制剂组第10日对神经功能恢复有显著的抑制作用（P<0.05），第5、10日对抓力恢复亦有较显著的抑制作用（P<0.05）。同时，与模型组比较，黄芩苷组孕酮水平显著升高（P<0.05），促卵泡激素和促黄体生成素水平有所下降（P>0.05）。结论 应用米非司酮对孕酮进行阻断后，黄芩苷的神经功能保护作用显著受到抑制，提示黄芩苷可能通过上调血清孕酮水平而发挥脑保护作用。

关键字：黄芩苷；脑缺血；血清孕酮；神经功能；大鼠

DOI：10.3969/j.issn.1005-5304.2016.07.017

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2016）07-0065-05

Regulation of Baicalin for Serum Progesterone Level and Its Effects on Neural Functions after Cerebral Ischemia in Rats LIU Jin-lin1， PAN Yan-shu1， LI Hai-yan1， CHENG Xiao-na1， WANG Dong-hui1， MU Tian-long2， LIU Yuan3 （1. College of Preclinical Medicine， Beijing University of Chinese Medicine， Beijing 100029， China； 2. Dongfang Hospital Affiliated to Beijing University of Chinese Medicine， Beijing 100078， China； 3. 302 Military Hospital of China， Beijing 100039， China）

Abstract： Objective To investigate the effects of baicalin on serum progesterone and related hormones in female normal and cerebral ischemia rats； To explore whether baicalin plays a role in cerebral protection of neurological functions by regulating progesterone levels. Methods With vaginal smear method， the adult estrus female SD rats were selected and divided into normal group， baicalin normal group， and molding groups. The left side of the middle cerebral artery of rats in the molding groups was blocked to establish the permanent middle cerebral artery occlusion （pMCAO）. After modeling， the rats were randomly divided into model group， baicalin treatment group， progesterone treatment group and progesterone inhibitor group. The baicalin normal group and baicalin treatment group were given intraperitoneal injection of baicalin solution； the normal group and model group were given normal saline of the same quantity； progesterone treatment group was given intramuscular injection of progesterone； progesterone inhibitor group was given intraperitoneal injection of baicalin solution and intragastric administration of mifepristone solution.

基金项目：国家重点基础研究发展计划（2012CB518602）；国家自然科学基金青年基金（81202832）

通讯作者：潘彦舒，E-mail：13911209998@163.com

The neurological function deficit scores were evaluated and rat forelimb holding power was detected by Grip Strength Meter respectively at different time points. Serum was taken from the rats and the progesterone and related hormones levels in the serum of every group were measured by ELISA. Results Compared with normal group， neurological functions of rats in molding groups were damaged， and neural functional behavior scores of different time points were the most strongly increased （P<0.001）， and rat forelimb holding power was the most strongly reduced （P<0.001）. 5 days after treating， baicalin showed the trend of improvement of neurological functions （P>0.05） and more significant improvement of the forelimb holding power （P<0.01）； 10 days after modeling， baicalin treatment group significantly increased neural functional behavior scorce （P<0.001） and the most significantly improved the forelimb holding power （P<0.001）. Compared with baicalin treatment group， the progesterone inhibitor group had a significant inhibitory effect on neural functional recovery （P<0.05） 10 days after modeling， and the group also had a significant inhibitory effect on the recovery of holding power （P<0.05） 5 days and 10 days after treating. At the same time， compared with the model group， progesterone level in baicalin treatment group increased significantly （P<0.05）， and FSH and LH decreased （P>0.05）. Conclusion After applying mifepristone to block progesterone， baicalin neurologic protection is significantly inhibited. The results demonstrated that baicalin may play a role in cerebral protection via up-regulating serum progesterone level.

Key words： baicalin； cerebral ischemia； serum progesterone； neurologic function； rats

脑血管疾病是当今社会严重危害人类健康的常见病和多发病，亦是导致死亡和残障的主要原因之一，缺血性脑卒中是最常见的脑卒中类型，占全部脑卒中的80%左右[1]。……