基于氧化应激探讨柴胡加龙骨牡蛎汤对心肌梗死合并焦虑大鼠海马保护作用机制  

Protective effect and mechanism of Chaihu Jia Longgu Muli Decoction on hippocampus of myocardial infarction with comorbid anxiety rats based on oxidative stress

作　　者：史金玉 王超[2] 贾子昊 周悦 赵海滨[2] SHI Jinyu;WANG Chao;JIA Zihao;ZHOU Yue;ZHAO Haibin(Beijing University of Chinese Medicine,Beijing 100029,China;Dongfang Hospital of Beijing University of Chinese Medicine,Beijing 100078,China)

机构地区：[1]北京中医药大学,北京100029 [2]北京中医药大学东方医院,北京100078

出　　处：《中华中医药杂志》2023年第10期4877-4882,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.82174332)。

摘　　要：目的:探讨柴胡加龙骨牡蛎汤对心肌梗死合并焦虑大鼠海马的保护作用机制。方法:将60只SPF级雄性SD大鼠随机分为空白组、假手术组、心肌梗死组、复合模型组和中药组。空白组为正常大鼠;心肌梗死组采用冠状动脉前降支结扎;假手术组只穿线不结扎;复合模型组和中药组,采用冠状动脉前降支结扎联合不确定空瓶刺激建立心肌梗死合并焦虑模型。心肌梗死术后第2天,中药组给予柴胡加龙骨牡蛎汤10 mL·kg^(-1)·d^(-1)灌胃,其余各组给予等量蒸馏水灌胃,每天1次,连续6 d。采用心脏超声评价心功能,行为学试验和海马神经递质评价焦虑样行为,病理染色观察海马组织变化。通过生化分析和ELISA检测血清和海马氧化应激参数,RT-qPCR检测海马Nrf2通路基因表达。结果:与复合模型组比较,中药组LVEF和LVFS升高、进入开放臂次数和开放臂停留时间增加、运动总距离和中心距离增加、5-HT和NE表达增加(P<0.01)。且中药组血清SOD、GSH和T-AOC表达增加(P<0.01),GSSG表达显著降低(P<0.01);海马ROS和8-OHdG表达降低,SOD表达显著增加(P<0.01),Nrf2和HO-1 mRNA表达显著增加(P<0.05,P<0.01),Keap1 mRNA表达显著降低(P<0.01)。结论:柴胡加龙骨牡蛎汤可能通过激活Nrf2通路,提高SOD、GSH和T-AOC的表达,减少ROS和8-OHdG的释放,抑制海马氧化应激,改善大鼠心功能和焦虑。Objective:To investigate the protective effect of Chaihu Jia Longgu Muli Decoction on the hippocampus of rats with myocardial infarction(MI)with comorbid anxiety.Methods:Sixty SPF grade male SD rats were randomly divided into control group,sham group,MI group,MI with comorbid anxiety group,and traditional Chinese medicine(TCM)group.The control group was normal rats,the MI group was ligated with the anterior descending coronary artery,the sham group was only threaded and not ligated.And in the complex group and the TCM groups,MI with comorbid anxiety model was established by ligation of the anterior descending coronary artery combined with uncertain empty bottle stimulation.On the second day of MI operation,the TCM group was given Chaihu Jia Longgu Muli Decoction 10 mL·kg^(-1)·d^(-1)by gavage,and the other groups were given the same volume of distlled water by gavage,once a day for 6 days.Cardiac function was evaluated by echocardiography,anxiety-like behavior was evaluated by behavioral tests and hippocampal neurotransmitters,and hippocampal tissue changes were observed by pathological staining.Serum and hippocampal oxidative stress parameters were measured by biochemical analysis and ELISA,and hippocampal Nrf2 pathway gene expression was detected by RT-qPCR.Results:Compared with the complex model group,LVEF and LVFS were elevated,the number of entries into the open arm and open arm dwell time were increased,total and central distance of movement were increased,and 5-HT and NE expression were increased in the TCM group(P<0.01).And in the TCM group,serum SOD,GSH and T-AOC expression increased(P<0.01)and GSSG expression decreased(P<0.01);hippocampal ROS and 8-OHdG expression decreased,and SOD expression increased(P<0.01),Nrf2 and HO-1 mRNA expression increased(P<0.05,P<0.01),Keap1 mRNA expression was decreased(P<0.01).Conclusion:Chaihu Jia Longgu Muli Decoction may improve cardiac function and anxiety in rats by activating the Nrf2 pathway,increasing the expression of SOD,GSH and T-AOC,reducing the release of ROS

关 键 词：柴胡加龙骨牡蛎汤 心肌梗死 焦虑 海马 氧化应激 

分 类 号：R285.5[医药卫生—中药学]