摘要： 目的 以“雌激素-雌激素受体”为靶点探讨左归丸对大鼠缺血后脑损伤的神经元保护机制。方法 将80只SD大鼠随机分为5组：假手术组、IR组、去势+IR组、去势+IR+中药组、去势+IR+雌二醇组。卵巢摘除法建立动物肾虚模型；线栓法制备大鼠大脑中动脉阻闭模型；采用穿越横桥法检测大鼠的运动功能；TTC染色测定脑梗死体积；HE染色观察大鼠脑皮质区神经元形态学改变；ELISA实验检测雌激素含量。免疫组化及Western blotting测定大鼠脑皮质区雌激素受体α（ERα）、雌激素受体β（ERβ）表达。结果 与假手术组比较，IR组大鼠运动及学习记忆功能明显下降（P < 0.05）。与IR比较，去势+IR组大鼠运动功能明显下降，梗死面积增大，存活神经元减少，大鼠脑皮质区神经元ERα、ERβ表达增加（P < 0.05）。与去势+IR组比较，去势+IR+中药组运动功能明显改善，梗死面积缩小，存活神经元增加，ERα、ERβ表达增加（P < 0.05）。与去势+IR+中药组比较，去势+IR+雌二醇组运动功能、梗死面积、存活神经元数量差异无统计学意义（P > 0.05）。结论 左归丸可能通过增加雌激素分泌和雌激素受体表达发挥对大鼠缺血后脑损伤的神经元保护作用。

左归丸对大鼠缺血后脑损伤的神经元保护机制

刘宏¹, 易娅静², 代巧妹¹, 杨婧¹, 仲丽丽², 李冀³

1. 黑龙江中医药大学基础医学院病理学教研室, 哈尔滨 150040;
2. 黑龙江中医药大学附属第一医院病理科, 哈尔滨 150040;
3. 黑龙江中医药大学基础医学院方剂学教研室, 哈尔滨 150040

收稿日期:2020-03-22出版日期:2021-01-30发布日期:2021-01-06
通讯作者:仲丽丽E-mail:zhll1979@126.com
作者简介:刘宏(1978-),女,副教授,博士.
基金资助:国家自然科学基金（82074288）；国家自然科学基金青年基金（81403288）；黑龙江省青年科学基金（QC2015102）；中国博士后科学基金（2016M591565）


关键词: 脑缺血, 再灌注, 雌激素, 左归丸, 大脑中动脉阻闭, 神经元, 保护作用
Abstract: Objective To explore the neuroprotective mechanism of Zuogui pill against brain injury after cerebral ischemia in rats by targeting the estrogen-estrogen receptor. Methods Eighty Sprague-Dawley rats were randomly divided into five groups:sham-operation,ischemia-reperfusion (IR),castration+IR,castration+IR+traditional Chinese medicine (TCM),and castration+IR+estradiol groups. Then,a mouse kidney deficiency model was established by performing ovariectomy,and a mouse middle cerebral artery occlusion model was established using the thread-bolt method. The motor function of rats was measured using the crossing-the-bridge method,infarct volume was measured using triphenyl tetrazolium chloride staining,morphological changes in cortical neurons were observed using hematoxylin and eosin staining,and estrogen content was measured using enzyme-linked immunosorbent assays. Levels of estrogen receptor (ER) α and ERβ in rat cerebral cortex were determined using immunohistochemistry and western blotting. Results The motor,learning,and memory functions in the IR group were significantly lower than those in the sham-operation group (P < 0.05). Additionally,motor function in the castrated+IR group decreased significantly,infarct size increased,the number of surviving neurons decreased,and ERα and ERβ increased than those in the IR group (P < 0.05). Moreover,the castration+IR+TCM group exhibited improved motor function,reduced infarct size,an increased number of surviving neurons,and elevated ERα and ERβ levels (P < 0.05) relative to the castration+IR group. Furthermore,there was no significant difference between the castration+IR+estradiol and castration+IR+TCM groups in terms of motor function,infarct area,or number of surviving neurons (P > 0.05). Conclusion Zuogui pill might play a neuroprotective role in rats with cerebral ischemic injury by increasing estrogen secretion and ER levels.
Key words: cerebral ischemia, reperfusion, estrogen, zuogui pill, middle cerebral artery occlusion, neuron, protective effect
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