GPR30在17β雌二醇减轻氯胺酮致发育期大鼠远期认知功能障碍中的作用  

Role of GPR30 in reduction of ketamine-induced long-term cognitive dysfunction by 17β estradiol in neonatal rats

作　　者：李建立[1] 蔚冬冬 吴晓倩[1] 何金华 Li Jianli;Yu Dongdong;Wu Xiaoqian;He Jinghua(Department of Anesthesiology,Hebei General Hospital,Shijiazhuang 050051,China)

机构地区：[1]河北省人民医院麻醉科,石家庄050051

出　　处：《中华麻醉学杂志》2021年第9期1097-1100,共4页Chinese Journal of Anesthesiology

基　　金：河北省自然科学基金面上项目(H2017307013)。

摘　　要：目的评价G蛋白偶联受体30(GPR30)在17β雌二醇减轻氯胺酮致发育期大鼠远期认知功能障碍中的作用。方法7日龄健康雄性SD大鼠30只,体重11~18 g,采用随机数字表法分为5组(n=6):对照组(C组)、氯胺酮组(K组)、17β雌二醇+氯胺酮组(EK组)、GPR30激动剂G1+氯胺酮组(G1K组)和GPR30抑制剂G15+17β雌二醇+氯胺酮组(G15EK组)。K组腹腔注射氯胺酮75 mg/kg,EK组皮下注射17β雌二醇600μg/kg,腹腔注射氯胺酮75 mg/kg,G1K组皮下注射G1200μg/kg和腹腔注射氯胺酮75 mg/kg,G15EK组皮下注射G15300μg/kg和17β雌二醇600μg/kg以及腹腔注射氯胺酮75 mg/kg,C组腹腔注射等容量生理盐水。每隔24 h注射1次,连续注射3 d。所有大鼠饲养至60日龄,采用Morris水迷宫实验检测大鼠认知功能。于水迷宫实验结束后处死大鼠取海马,采用ELISA法检测海马乙酰胆碱酯酶(AChE)和乙酰胆碱(ACh)的含量。结果与C组比较,K组大鼠第3~5天逃避潜伏期延长,穿越平台次数及靶象限停留时间百分比减少,海马AChE含量增加,ACh含量减少(P<0.05);与K组比较,EK组和G1K组大鼠第3~5天逃避潜伏期缩短,穿越平台次数及靶象限停留时间百分比增加,海马AChE含量减少,ACh含量增加(P<0.05);与EK组和G1K组比较,G15EK组大鼠第3~5天逃避潜伏期延长,穿越平台次数及靶象限停留时间百分比减少,海马AChE含量增加,ACh含量减少(P<0.05)。结论GPR30参与了17β雌二醇减轻氯胺酮致发育期大鼠远期认知功能障碍的过程,与调节海马AChE和ACh含量有关。Objective To evaluate the role of G protein-coupled receptor 30(GPR30)in reduction of ketamine-induced long-term cognitive dysfunction by 17βestradiol in neonatal rats.Methods Thirty healthy male Sprague-Dawley rats,aged 7 days,weighing 11-18 g,were divided into 5 groups(n=6 each)using a random number table method:control group(group C),ketamine group(group K),17βestradiol plus ketamine group(group KE),GPR30 agonist G1 plus ketamine group(group G1K)and GPR30 inhibitor G15 plus 17βestradiol plus ketamine group(group G15EK).Ketamine 75 mg/kg was intraperitoneally injected in group K.In group EK,17βestradiol 600μg/kg was subcutaneously injected,and ketamine 75 mg/kg was intraperitoneally injected.In group G1K,G1200μg/kg was subcutaneously injected,and ketamine 75 mg/kg was intraperitoneally injected.In group G15EK,G15300μg/kg and 17βestradiol 600μg/kg were subcutaneously injected,and ketamine 75 mg/kg was intraperitoneally injected.The equal volume of normal saline was intraperitoneally given in group C.The injection was performed every 24 h for 3 consecutive days.All the rats were allowed to grow up till postnatal day 60,and then Morris water maze test was performed to evaluate their spatial learning and memory function.The rats were sacrificed after the end of Morris water maze test,and hippocampi were removed for determination of contents of acetyl cholinesterase(AChE)and acetylcholine(ACh)by enzyme-linked immunosorbent assay.Results Compared with group C,the escape latency was significantly prolonged on the 3-5 training days,the frequency of crossing the platform and percentage of time of staying at the target quadrant were decreased,the content of AChE was increased,and the content of ACh was decreased in group K(P<0.05).Compared with group K,the escape latency was significantly shortened on the 3-5 training days,the frequency of crossing the platform and percentage of time of staying at the target quadrant were increased,the content of AChE was decreased,and the content of ACh was increased in EK and

关 键 词：受体 G-蛋白偶联 雌二醇 氯胺酮 认知障碍 

分 类 号：R749.1[医药卫生—神经病学与精神病学]