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癫痫清颗粒改善AD模型小鼠血脑屏障损伤的作用研究
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| 篇名： | 癫痫清颗粒改善AD模型小鼠血脑屏障损伤的作用研究 |
| TITLE： | Improvement effects of Dianxianqing granule on blood-brain barrier injury in Alzheimer ’s disease model mice |
| 摘要： | 目的 研究癫痫清颗粒通过调控核苷酸结合域样受体蛋白3（NLRP3）炎症小体信号通路对阿尔茨海默病（AD）模型小鼠血脑屏障（BBB）损伤的改善作用。方法将125只小鼠按体质量随机分为假手术组（n＝25）和造模组（n＝100）。造模组小鼠采用侧脑室注射β-淀粉样蛋白25～35的方法复制AD模型；假手术组小鼠同法注射生理盐水。选取造模成功的100只小鼠，按体质量随机分为模型组、盐酸多奈哌齐片组（阳性对照1，1.3mg/kg，灌胃给药）、MCC950组[阳性对照2（选择性NLRP3抑制剂），10mg/kg，腹腔注射给药]和癫痫清颗粒组（以生药总量计12.48g/kg，灌胃给药），每组25只。造模后第2天，各给药组小鼠给予相应药物，每天1次，连续21d；假手术组和模型组小鼠灌胃水并腹腔注射生理盐水。末次给药后，采用Y迷宫实验检测小鼠的学习记忆能力，采用伊文思蓝渗漏实验测定小鼠BBB通透性；检测小鼠脑组织中NLRP3、离子钙接头蛋白（IBA-1）、核转录因子κB（NF-κB）p65、p53上调凋亡调控因子（PUMA）、咬合蛋白（ocln）、闭锁小带蛋白1（ZO-1）、紧密连接蛋白5（cldn5）的表达水平。结果与模型组比较，各给药组小鼠的自发交替反应率和脑组织中ocln、cldn5、ZO-1蛋白表达水平均显著升高（P＜0.05或P＜0.01），脑组织内的伊文思蓝含量及NLRP3、IBA-1、PUMA、NF-κBp65蛋白表达水平均显著降低（P＜0.05或P＜0.01）。结论癫痫清颗粒可通过抑制NLRP3炎症小体信号通路起到改善AD模型小鼠BBB损伤的作用。 |
| ABSTRACT： | OBJECTIVE To study the impr ovement effects of Dianxianqing granule on blood-brain barrier （BBB）injury in Alzheimer’s disease （AD）model mice by regulating NLR family pyrin domain containing 3（NLRP3）inflammasome signaling pathway. METHODS Totally 125 mice were randomly divided into sham operation group （n＝25）and modeling group （n＝100） by body weight. AD model was induced by intracerebroventricular injection of β-amyloid 25-35 in model group. Sham operation group was given normal saline with same method. The 100 model mice were randomly divided into model group ，Donepezil hydrochloride tablets group （positive control 1，1.3 mg/kg，i.g.），MCC950 group [positive control 2（selective NLRP 3 inhibitor），10 mg/kg，i.p.] and Dianxianqing granule group （12.48 g/kg by crude drug ，i.g.）by body weight ，with 25 mice in each group. Second day after modeling ，administration groups were given relevant medicine ，once a day ，for consecutive 21 d. Sham operation group and model group were given intragastric administration of water and intraperitoneal injection of normal saline. At last administration，the learning and memory ability was determined by Y maze test ，and blood-brain barrier permeability was measured by Evans blue leakage assay. The expressions of NLRP 3，anti-ionized calcium-binding adapter molecule 1（IBA-1），nuclear factor kappa B （NF-κB）p65，p53 upregulated modulator of apoptosis （PUMA），occludin（ocln），zonula occluden- 1（ZO-1）and claudin-5 （cldn5） in cerebral tissue were determined. RESULTS Compared with model group ， spontaneous alternate response rate ，protein expressions of ocln ，cldn5 lnzyxyqy2003@163.com and ZO- 1 in cerebral tissue were increased significantly in administration groups （P＜0.05 or P＜0.01）；Evans blue E-mail：jiadg2003@126.com content and protein expressions of NLRP 3，IBA-1，PUMA and NF-κB p65 in cerebral tissue were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Dianxianqing granule can improve BBB injury of AD model m ice by inhibiting NLRP 3 inflammasome signaling pathway. |
| 期刊： | 2022年第33卷第09期 |
| 作者： | 齐越，李昭，侯侠，黄培池，贾冬，杨彩瑜，董笑博，房小楠，明彩荣 |
| AUTHORS： | QI Yue， LI Zhao，HOU Xia，HUANG Peichi，JIA Dong，YANG Caiyu，DONG Xiaobo，FANG Xiaonan，MING Cairong |
| 关键字： | 癫痫清颗粒；阿尔茨海默病；血脑屏障；核苷酸结合域样受体蛋白 3炎症小体；紧密连接蛋白 |
| KEYWORDS： | Dianxianqing granule ；Alzheimer’s disese ；blood-brain barrier ；NLRP3 inflammasome；tight junction proteins |
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