Page 46 - 南京医科大学学报自然科学版

南京医科大学学报（自然科学版） 第41卷第4期
·516 · Journal of Nanjing Medical University（Natural Sciences） 2021年4月

·基础医学·

α⁃FMH 抑制小胶质细胞的活化改善大鼠相关炎症与认知功能

障碍

侍崇龙，董洪权，金文杰 *
南京医科大学第一附属医院麻醉科，江苏 南京 210029

［摘 要］ 目的：在体探究组氨酸脱羧酶抑制剂α⁃FMH对脂多糖（lipopolysaccharide，LPS）引起的大鼠相关炎症及认知功能障
碍的影响。方法：48只SD雄性大鼠随机分为4组，每组12只，分别为Control组、α⁃FMH组、LPS组、α⁃FMH+LPS组。在立体定
位仪下行大鼠右侧侧脑室置管，恢复1周后置于逃避恐惧实验仪器中学习。然后将α⁃FMH或等体积的生理盐水定向注入大鼠
右侧侧脑室，给药后30 min行LPS（1 mg/kg）腹腔注射，1 d后行为学实验评估大鼠的逃避恐惧能力；免疫组化检测海马区小胶
质细胞的活化情况；ELISA法检测白介素⁃6和肿瘤坏死因子⁃α的表达量。结果：大鼠腹腔注射LPS后6 h海马区组胺表达明显
增多，24 h 内皆高于基础水平。与 Control 组相比，LPS 组大鼠海马区小胶质细胞活化及上述炎症因子的表达均增加（P <
0.01），且LPS组大鼠的僵立时间明显降低（P < 0.01）。与LPS组相比，α⁃FMH+LPS组大鼠海马区小胶质细胞活化及炎症因子
的表达明显降低（P < 0.01），且α⁃FMH+LPS组大鼠的僵立时间明显增加（P < 0.01）。结论：组氨酸脱羧酶抑制剂α⁃FMH通过抑
制小胶质细胞的活化改善LPS诱导的大鼠相关炎症与认知功能障碍。
［关键词］ α⁃FMH；小胶质细胞；白介素⁃6；肿瘤坏死因子⁃α；组胺；脂多糖
［中图分类号］ R742 ［文献标志码］ A ［文章编号］ 1007⁃4368（2021）04⁃516⁃06
doi：10.7655/NYDXBNS20210407

α⁃FMH alleviates LPS⁃induced inflammation and cognitive impairment in rats by inhibiting

the activation of microglia
*
SHI Chonglong，DONG Hongquan，JIN Wenjie
Department of Anesthesiology，the First Affiliated Hospital of Nanjing Medical University，Nanjing 210029，China

［Abstract］ Objective：To explore the effects of histidine decarboxylase inhibitors on lipopolysaccharide（LPS）⁃ induced
inflammation and cognitive impairment in rats in vivo. Methods：Forty⁃eight SD male rats were randomly divided into 4 groups with 12
rats in each group：control group，α⁃FMH group，LPS group and α⁃FMH+LPS group. Catheters were placed in the right lateral ventricle
of rats with a stereotactic instrument，and a week after recovery，they were placed in an escape fear experimental instrument to learn.
Then α ⁃ FMH and the same volume of normal saline were directionally injected into the lateral ventricle of rats. Half an hour after
administration，LPS（1 mg/kg）was injected intraperitoneally. A day later，the ability of rats to escape fear was evaluated by behavioral
experiments. The activation of microglia in the hippocampus was detected by immunohistochemistry. The expression of interleukin 6 and
tumor necrosis factor α was detected by ELISA method. Results：After intraperitoneal injection of LPS，the expression of histamine in
hippocampus began to increase significantly at 6 h，and was higher than the basic level within 24 h. Compared with the control group，the
activation of microglia and the expression of inflammatory factors mentioned above in the hippocampus of the LPS group were increased
（P < 0.01），and the freezing time of the LPS group was significantly decreased（P < 0.01）. Compared with LPS group，the activation of
microglia and the expression of the inflammatory factors in the hippocampus of α⁃FMH+LPS group were significantly decreased（P <
0.01），and the freezing time of α⁃FMH+LPS group was significantly increased（P < 0.01）. Conclusion：Histidine decarboxylase inhibitor α
⁃FMH can alleviate LPS⁃induced inflammation and cognitive impairment in rats by inhibiting the activation of microglia.
［Key words］ α⁃FMH；mcroglia；IL⁃6；TNF⁃α；histamine；LPS
［J Nanjing Med Univ，2021，41（04）：516⁃521］

［基金项目］ 国家自然科学基金青年项目（81701375）；江苏省自然科学基金青年项目（BK20171088）
∗
通信作者（Corresponding author），E⁃mail：kinwj210@126.com