加味温胆汤对抑郁模型大鼠小胶质细胞炎症反应的抑制作用及机制研究  

Inhibitory effect and mechanism of Jiawei Wendan Decoction on inflammation of microglia in depressed rats

作　　者：徐磊 张丽萍[1] 宋瑞雯[1] 陈颖[1] 王慎军 XU Lei;ZHANG Li-ping;SONG Rui-wen;CHEN Ying;WANG Shenjun(Tianjin University of Traitional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]天津中医药大学,天津301617

出　　处：《中华中医药杂志》2021年第7期3832-3837,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81673911)。

摘　　要：目的:探讨加味温胆汤调节小胶质细胞抑制炎症反应发挥抗抑郁的作用机制。方法:选用8周龄SPF级SD健康雄性大鼠60只,适应性喂养1周,造模前进行旷场实验筛选40只行为学评分相近的大鼠,按随机数表随机分为空白组、模型组、加味温胆汤组、氟西汀组,每组10只。除空白组外其余各组给予21d慢性不可预知性温和刺激(CUMS),造模结束后模型组予0.9%氯化钠溶液2mL·kg-1·d-1,加味温胆汤组予加味温胆汤12g·kg-1·d-1,氟西汀组予氟西汀1.8mg·kg-1·d-1,均连续灌胃给药28d。给药结束后,采用透射电镜检测大鼠前额叶皮质神经胶质细胞超微结构变化,采用免疫组化观察前额叶皮质小胶质的形态结构及其特异性标志物离子钙结合衔接分子1(Iba1)阳性细胞数变化,RT-PCR检测整合素11b(CD11b)、Iba1 mRNA表达变化,ELISA检测血清白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)的含量变化。结果:与空白组比较,模型组前额叶皮质神经胶质细胞超微结构损害明显,小胶质细胞突起短缩,胞体肿胀,Iba1阳性细胞数显著增多(P<0.01),CD11b、Iba1 mRNA相对表达量及血清IL-1β、IL-6、TNF-α显著增加(P<0.01);与模型组比较,加味温胆汤组和氟西汀组神经胶质细胞超微结构的形态损伤明显减轻,小胶质细胞细胞突起变长,胞体肿胀减轻,Iba1阳性细胞数显著降低(P<0.01),CD11b、Iba1 mRNA表达量及血清IL-1β、IL-6、TNF-α含量显著降低(P<0.01,P<0.05)。结论:加味温胆汤可通过抑制小胶质细胞炎症反应,减轻神经胶质细胞超微结构损伤,发挥抗抑郁作用。Objective: To explore the anti-depression mechanism of Jiawei Wendan Decoction in regulating the inflammatory reaction of microglia. Methods: Sixty 8-week-old SPF SD healthy male rats were selected and fed adaptively for one week. Before modeling, 40 rats with similar behavioral scores were screened by open field experiment, and randomly divided into blank group, model group, Jiawei Wendan Decoction group and fluoxetine group, with 10 rats in each group. All groups except the blank group were given chronic unpredictable mild stimulation(CUMS) for 21 days. After modeling, the model group was given 0.9% sodium chloride solution 2 mL·kg-1·d-1, the modified Wendan Decoction group was given 12 g·kg-1·d-1, and the fluoxetine group was given fluoxetine 1.8 mg·kg-1·d-1, all of them were administered by gavage continuously for 28 days. After administration, the ultrastructural changes of glial cells in rat prefrontal cortex were detected by transmission electron microscope, the morphological structure of microglia in prefrontal cortex and the changes of specific marker ionized calcium binding adapter 1(Iba1) positive cells were observed by immunohistochemistry, the expression of integrin 11 b(CD11 b) and Iba1 mRNA were detected by RT-PCR, and serum interleukin(IL)-1β, IL-6, tumor necrosis factor-α(TNF-α) were detected by ELISA. Results: Compared with the blank group, in the model group, the ultrastructure of glial cells in prefrontal cortex was obviously damaged, the process of microglia was shortened, the cell body was swollen, the number of Iba1 positive cells increased significantly(P<0.01), the relative expression of CD11 b, Iba1 mRNA and serum IL-1β, IL-6 and TNF-α increased significantly(P<0.01). Compared with the model group, the morphological damage of glial cell ultrastructure in Jiawei Wendan Decoction group and fluoxetine group was significantly reduced, the process of microglial cells became longer, the swelling of cell body was reduced, the number of Iba1 positive cells was significantly decreased(

关 键 词：加味温胆汤 抑郁症 小胶质细胞 炎症因子 机制 

分 类 号：R285.5[医药卫生—中药学]