基于Bcl-2/Bax/caspase-3通路探讨熟地黄对注意缺陷多动障碍大鼠纹状体神经元凋亡的影响  

Effects of Rehmanniae Radix Praeparata on striatal neuronal apoptosis in ADHD rats via Bcl-2/Bax/caspase-3 pathway

作　　者：王静[1] 朱康琳 倪新强 蔡文华[1] 杨宇婷 章嘉琦 周翀 史美君 WANG Jing;ZHU Kang-lin;NI Xin-qiang;CAI Wen-hua;YANG Yu-ting;ZHANG Jia-qi;ZHOU Chong;SHI Mei-jun(the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine,Shenzhen 518033,China;Shenzhen Traditional Chinese Medicine Hospital,Shenzhen 518033,China;the Seventh Afiliated Hospital of Sun Yat-sen University,Shenzhen 518107,China)

机构地区：[1]广州中医药大学第四临床医学院,广东深圳518033 [2]深圳市中医院,广东深圳518033 [3]中山大学附属第七医院,广东深圳518107

出　　处：《中国中药杂志》2025年第3期750-757,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(82074492,82374517);深圳市科技创新委员会项目(JCYJ20230807094808017);深圳市中医院“3030计划”中医临床研究项目(G3030202125)。

摘　　要：基于B淋巴细胞瘤-2(Bcl-2)/Bcl-2相关X蛋白(Bax)/半胱氨酸蛋白酶-3(caspase-3)信号通路探讨熟地黄对注意缺陷多动障碍(ADHD)大鼠纹状体神经元凋亡的影响。将24只3周龄雄性自发性高血压病大鼠(SHR)随机分为模型组、哌甲酯组(2 mg·kg^(-1)·d^(-1))和熟地黄组(2.4 mg·kg^(-1)·d^(-1)),同周龄雄性WKY大鼠设为正常组,每组8只,连续灌胃给药28 d。记录每组体质量和摄食量;旷场实验、高架十字迷宫测试评估大鼠多动、冲动行为;尼氏染色法检测纹状体神经元及尼氏体变化;原位末端标记法(TUNEL)荧光染色检测纹状体细胞凋亡;免疫印迹法(Western blot)检测纹状体中Bcl-2、Bax、caspase-3蛋白的表达量。结果显示,与模型组相比,熟地黄可显著降低SHR大鼠在旷场实验中的总运动距离、平均运动速度和中心区停留时间,显著减少在高架十字迷宫中进入开臂的次数比、开臂停留时间和探头次数,明显增加纹状体神经元尼氏体,显著下调凋亡指数,显著升高Bcl-2蛋白表达及Bcl-2/Bax比值,降低Bax、caspase-3蛋白表达。总之,熟地黄可减少ADHD大鼠的多动、冲动行为,其作用可能与调控纹状体Bcl-2/Bax/caspase-3信号通路,增强纹状体神经元抗凋亡能力有关。This study investigated the effects of Rehmanniae Radix Praeparata on striatal neuronal apoptosis in rats with attention deficit hyperactivity disorder(ADHD) based on the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X protein(Bax)/caspase-3 signaling pathway. Twenty-four 3-week-old male spontaneously hypertensive rats(SHR) were randomly divided into a model group, a methylphenidate group(2 mg·kg^(-1)·d^(-1)), and a Rehmanniae Radix Praeparata group(2.4 mg·kg^(-1)·d^(-1)). Age-matched male Wistar Kyoto(WKY) rats were used as the normal control group, with 8 rats in each group. The rats were administered by gavage for 28 days. Body weight and food intake were recorded for each group. The open field test and elevated plus maze test were used to assess hyperactivity and impulsive behaviors. Nissl staining was used to detect changes in striatal neurons and Nissl bodies. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) fluorescence staining was used to detect striatal cell apoptosis. Western blot was employed to detect the expression levels of Bcl-2, Bax, and caspase-3 proteins in the striatum. The results showed that compared with the model group, Rehmanniae Radix Praeparata significantly reduced the total movement distance, average movement speed, and central area residence time in the open field test, and significantly reduced the ratio of open arm entries, open arm stay time, and head dipping in the elevated plus maze test. Furthermore, it increased the number of Nissl bodies in striatal neurons, significantly downregulated the apoptosis index, significantly increased Bcl-2 protein expression and the Bcl-2/Bax ratio, and reduced Bax and caspase-3 protein expression. In conclusion, Rehmanniae Radix Praeparata can reduce hyperactivity and impulsive behaviors in ADHD rats. Its mechanism may be related to the regulation of the Bcl-2/Bax/caspase-3 signaling pathway in the striatum, enhancing the anti-apoptotic capacity of striatal neurons.

关 键 词：熟地黄 注意缺陷多动障碍 纹状体 Bcl-2 Bax CASPASE-3 神经元凋亡 

分 类 号：R285.5[医药卫生—中药学]