基于JNK/c-Myc/p53信号通路探讨酸枣仁汤对抑郁模型大鼠的干预作用  

Intervention Effect of Suanzaoren Tang on Depression Model Rats Based on JNK/c-Myc/p53 Pathway

作　　者：杜帅霖 郝志成 张策 国荠元 田旭升[2] DU Shuailin;HAO Zhicheng;ZHANG Ce;GUO Jiyuan;TIAN Xusheng(Graduate School of Heilongjiang University of Chinese Medicine,Harbin 150040,China;Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学研究生院,哈尔滨150040 [2]黑龙江中医药大学,哈尔滨150040

出　　处：《中国实验方剂学杂志》2025年第5期12-19,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：黑龙江省自然科学基金项目(H2018057);黑龙江省中医药科研项目(ZHY2023-143)。

摘　　要：目的:探讨建立孤养结合慢性不可预见性温和应激(CUMS)引起的抑郁模型大鼠后酸枣仁汤的干预作用,观察该方对c-Jun氨基末端激酶(JNK)/原癌基因蛋白(c-Myc)/调节蛋白53(p53)信号通路的影响,揭示其潜在的功能机制。方法:72只雄性SD大鼠采用随机数字表法进行随机分组,分为空白组,模型组,氟西汀组(3.6 mg·kg^(-1))和酸枣仁汤高、中、低剂量组(10、5、2.5 g·kg^(-1)),每组12只,采用孤养结合CUMS方法诱导抑郁大鼠模型,随后使用氟西汀和不同剂量的酸枣仁汤连续治疗28 d,并观察各组大鼠糖水消耗、旷场实验得分、蛋白免疫印迹法(Western blot)和免疫组化法(IHC)分析JNK/c-Myc/p53信号通路的关键蛋白表达,原位末端标记法(TUNEL)检测用来评估治疗效果对大鼠大脑海马内凋亡细胞数量的影响。结果:与空白组比较,模型组大鼠糖水偏好指数显著降低(P<0.01);旷场实验中水平运动加垂直运动总分降低(P<0.01);海马JNK、c-Myc、p53蛋白表达显著上升(P<0.01);大鼠海马TUNEL阳性细胞增加(P<0.01)。与模型组比较,酸枣仁汤高、中剂量组和氟西汀组糖水偏爱指数和旷场实验中水平运动加垂直运动总分均大幅度上升(P<0.05,P<0.01);酸枣仁汤高、中、低剂量组及氟西汀组大鼠JNK、c-Myc、p53蛋白表达均大幅度下降(P<0.05,P<0.01);大鼠海马TUNEL阳性细胞降低(P<0.01)。结论:酸枣仁汤可调节抑郁模型大鼠JNK/c-Myc/p53在海马中的表达,其抗抑郁机制可能与对海马神经元的保护作用有关。Objective:To investigate the intervention effects of Suanzaoren Tang on depression model rats induced by isolation combined with chronic unpredictable mild stress(CUMS),and to examine its influence on the c-Jun N-terminal kinase(JNK)/proto-oncogene protein(c-Myc)/tumor suppressor protein 53(p53)signaling pathway,thereby revealing its potential functional mechanism.Methods:A total of 72 male SD rats were randomly divided into six groups using a strict random number table:blank group,model group,fluoxetine group(3.6 mg·kg^(-1)),and high-,medium-,and low-dose Suanzaoren Tang groups(10,5,2.5 g·kg^(-1)),with 12 rats in each group.A depression model was established using isolation combined with CUMS.Fluoxetine and different doses of Suanzaoren Tang were administered continuously for 28 days.Behavioral indicators such as sucrose water consumption and open field test scores were recorded.Western blot and immunohistochemistry(IHC)were employed to analyze the expression of key proteins in the JNK/c-Myc/p53 signaling pathway,and the terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay was used to evaluate the number of apoptotic cells in the hippocampus.Results:Compared with the blank group,the model group exhibited a significantly reduced sucrose preference index(P<0.01),a lower total score of horizontal and vertical movements in the open field test(P<0.01),significantly increased expression of JNK,c-Myc,and p53 proteins in the hippocampus(P<0.01),and a higher number of TUNEL-positive cells in the hippocampus(P<0.01).Compared with the model group,the sucrose preference index and the total score of horizontal and vertical movements in the open field test significantly increased in the high-and medium-dose Suanzaoren Tang groups and the fluoxetine group(P<0.05,P<0.01).The expression of JNK,c-Myc,and p53 proteins significantly decreased in all Suanzaoren Tang groups(high,medium,and low doses)and the fluoxetine group(P<0.05,P<0.01).The number of TUNEL-positive cells in the hippocampus also significantly d

关 键 词：酸枣仁汤 抑郁症 c-Jun氨基末端激酶(JNK)/原癌基因蛋白(c-Myc)/调节蛋白53(p53)信号通路 大鼠 海马 

分 类 号：R259[医药卫生—中西医结合] R289[医药卫生—中医内科学] R242[医药卫生—中医学]