复方高滋斑片对抑郁大鼠海马NLRP3炎症小体的影响  

Effects of Compound Gaoziban Tablet on NLRP3 inflammasome in hippocampus of depressed rats

作　　者：肖敏 韩正茹 游秋云 昝俊峰 石雷 尤朋涛 XIAO Min;HAN Zhengru;YOU Qiuyun;ZAN Junfeng;SHI Lei;YOU Pengtao(Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine,College of Pharmacy,Hubei University of Chinese Medicine,Hubei Wuhan 430065,China)

机构地区：[1]湖北中医药大学药学院,中药资源与中药化学省级重点实验,湖北武汉430065

出　　处：《中国医院药学杂志》2024年第18期2115-2121,共7页Chinese Journal of Hospital Pharmacy

基　　金：湖北省自然科学基金(编号:No.2018CFB657)。

摘　　要：目的:研究复方高滋斑片(Compound Gaoziban Tablets,CGZBT)对抑郁大鼠的缓解作用和海马NLRP3炎症小体的潜在影响。方法:适应性喂养1周后根据0 weeks糖水偏好率将大鼠随机分为Control组、CUMS组、CGZBT-L组(0.4g·kg^(–1))、CGZBT-M组(0.8 g·kg^(–1))、CGZBT-H组(1.6 g·kg^(–1))、Fluoxetine组,每组12只。SD大鼠造模6周建立慢性不可预知轻度应激(CUMS)抑郁模型,从第5周开始在CUMS造模同时给予相应药物干预2周。最后1天对大鼠进行糖水偏好实验、旷场实验、强迫游泳实验。麻醉后对大鼠海马体、血清进行取材,苏木精-伊红染色法观察海马体CA1区神经元细胞的变化。用ELISA法检测血清中肿瘤坏死因子α(TNF-α)、白介素-1β(IL-1β)表达水平。Western blot法检测海马体中核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、凋亡相关斑点样蛋白(ASC)、半胱氨酸天冬氨酸蛋白酶-1(Caspase-1)、白细胞介素-1β前体(pro-IL-1β)、IL-1β、白介素-18(IL-18)的表达水平。结果:与CUMS组相比,CGZBT各剂量组旷场移动总距离显著增加(P<0.01),强迫游泳不动时间减少(P<0.01或P<0.05);CGZBT-M组和CGZBT-H组大鼠的糖水偏好率显著增加(P<0.01)。CGZBT可缓解CUMS大鼠海马体CA1区神经元细胞的损伤和降低血清中TNF-α、IL-1β的含量(P<0.01或P<0.05)。与CUMS组相比,CGZBT各剂量组大鼠海马中ASC、Caspase-1、IL-1β、的蛋白表达显著下调(P<0.01或P<0.05);CGZBT-M组和CGZBT-H组大鼠NLRP3、IL-18蛋白表达显著下调(P<0.01或P<0.05)。结论:CGZBT可缓解抑郁大鼠的抑郁症状并抑制海马体中NLRP3炎性小体的表达。OBJECTIVE To explore the alleviating effect of Compound Gaoziban Tablets (CGZBT) on depressive rats and examine the potential effects of NLRP3 inflammasome in hippocampus.METHODS After 1-week adaptive feeding,72Sprague-Dawley (SD) rats were randomized into 6 groups of control,CUMS,CGZBT-L (0.4 g·kg^(–1)),CGZBT-M (0.8 g·kg^(–1)),CGZBT-H (1.6 g·kg^(–1)) and fluoxetine based upon 0 weeks sugar-water preference (n=12 each).A depression model of chronic unpredictable mild stress (CUMS) was established after 6-week modeling.Appropriate pharmacological interventions were administered for 2 weeks starting from Week 5.Sugar preference,open field and forced swimming tests were conducted on the last day.Hippocampal and serum samples were collected after anesthesia.Hematoxylin-easin staining detected the changes of neurons in the CA1 of hippocampal tissue.The expression level of tumor necrosis factor-α (TNF-α) and interleukin-β (IL-1β) in serum were detected by enzyme-linked inmunosorbent assacy.The expression levels of nod-like receptor protein 3 (NLRP3),apoptosis-associated speck-like protein containing a CARD (ASC),cysteinyl aspartate specific proteinase-1 (caspase-1),interleukin-1β precursor (pro-IL-1β),IL-1β and interleukin-18 (IL-18) in hippocampus were detected by Western blot.RESULTS As compared with CUMS group,total distance in open field spiked markedly (P<0.01) and immobile time of forced swimming declined (P<0.01 or P<0.05) in each dose group of CGZBT;sugar preference rate rose obviously in CGZBT-M and CGZBT-H groups (P<0.01).CGZBT alleviated the injury of neuronal cells in CA1 region of hippocampus and lowered the serum levels of TNF-α and IL-1β (P<0.01 or P<0.05).As compared with CUMS group,protein expressions of ASC,caspase-1 and IL-1β were markedly down-regulated in hippocampus of rats in each dose group of CGZBT (P<0.01 or P<0.05);and protein expressions of NLRP3 and IL-18 were significantly down-regulated in hippocampus of rats in CGZBT-M and CGZBT-H groups(P<0.01 or P<0.05).CONCLUSION CG

关 键 词：复方高滋斑片 抑郁症 炎症小体 海马 

分 类 号：R966[医药卫生—药理学]