养心汤调控TLR4/NLRP3信号通路治疗抑郁症大鼠机制  

Mechanism of Yangxin decoction on depression model rats based on TLR4/NLRP3 signaling pathway

作　　者：蒋钰涵 王锐[1] 于钦明[1] JIANG Yuhan;WANG Rui;YU Qinming(Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学,黑龙江哈尔滨150040

出　　处：《陕西中医》2025年第3期306-310,共5页Shaanxi Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(82074271)。

摘　　要：目的:探讨养心汤通过TLR4/NLRP3信号通路干预CUMS抑郁模型大鼠的作用机制。方法:50只雄性SD大鼠随机分为对照组、模型组、氟西汀组、养心汤低剂量组、养心汤高剂量组。采用慢性不可预知性刺激建立CUMS大鼠模型,各组大鼠均通过灌胃给药,1次/d,连续灌胃3周。养心汤低剂量组、养心汤高剂量组、氟西汀组大鼠给予相应药物,对照组和模型组给予0.9%氯化钠溶液。糖水偏好、旷场、悬尾和强迫游泳实验检测大鼠抑郁样症状;ELISA法检测大鼠海马组织白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)水平;Hoechst染色检测大鼠海马神经元凋亡程度;RT-PCR和Western blot法检测大鼠脑组织通路因子TLR4、NLRP3与Caspase-1的表达。结果:与对照组相比,模型组大鼠蔗糖偏好、旷场、悬尾、强迫游泳实验结果均呈抑郁样症状。海马组织中IL-1β、IL-18水平升高,神经元出现大量凋亡,TLR4、NLRP3与Caspase-1蛋白与mRNA表达上升,差异有统计学意义(P<0.01)。与模型组相比,养心汤低剂量组、养心汤高剂量组、氟西汀组大鼠抑郁样症状得到显著改善,IL-1β、IL-18降低,差异有统计学意义(均P<0.05)。与模型组相比,养心汤低剂量组、养心汤高剂量组、氟西汀组大鼠海马神经元凋亡得到改善,TLR4、NLRP3、Caspase-1蛋白与mRNA的表达降低,差异有统计学意义(均P<0.05)。结论:养心汤可有效改善CUMS大鼠抑郁样行为,其机制可能与调控TLR4/NLRP3信号通路、缓解炎症反应有关。Objective:To investigate effect of Yangxin decoction on CUMS depressive model rats by regulating TLR4/NLRP3 signaling pathway.Methods:Fifty male SD rats were randomly divided into control group,model group,fluoxetine group and Yangxin decoction low-dose and high-dose groups.CUMS rat model were established by chronic unpredictability stimulation.All rats in each group were given corresponding drug by intragastrial administration.Yangxin decoction low-dose and high-dose group and fluoxetine group were given corresponding drug,and the control group and model group were given normal saline by intragastrial administration once a day for 3 weeks.Depression-like symptoms were detected by sugar water preference,open field,tail suspension and forced swimming.The levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)in rat hippocampus were detected by ELISA.Hoechst staining were used to detect apoptosis of hippocampal neurons.The expression of pathway factors TLR4,NLRP3 and Caspase-1 were detected by RT-PCR and Western blot.Results:Compared with the control group,the model group showed significant depression-like symptoms in sucrose preference,open field,tail suspension and forced swimming tests.The levels of IL-1βand IL-18 in hippocampus were significantly increased,difference statistically significant(all P<0.01),and a large number of neurons suffered apoptosis.The protein and mRNA expressions of TLR4,NLRP3 and Caspase-1 were significantly increased(all P<0.01).Compared with the model group,depression-like symptoms were significantly improved in Yangxin decoction low dose,high dose and fluoxetine groups,IL-1βand IL-18 levels were decreased,difference statistically significant(all P<0.05),and hippocampal neuron apoptosis were improved.The protein and mRNA expressions of TLR4,NLRP3 and Caspase-1 were significantly decreased,difference statistically significant(all P<0.05).Conclusion:Yangxin decoction can effectively improve depression-like behavior in CUMS rats,and its mechanism may be related to regulating TLR4/NLRP

关 键 词：抑郁症 养心汤 Toll样受体4/NOD样受体蛋白3信号通路 慢性不可预知性刺激 炎症反应 抑郁样症状 

分 类 号：R256[医药卫生—中医内科学]