参仙升脉口服液对病态窦房结综合征模型小鼠认知功能的影响及机制研究  

Effect and Mechanism of Shenxian Shengmai Oral Liquid(参仙升脉口服液)on Cognitive Function of Sick Sinus Syndrome Model Mice

作　　者：李令康 张恒 郝苗[1] 陈克研[2] 任路[1] 齐静[3] 陈晨 刘壮 侯平[3] LI Lingkang;ZHANG Heng;HAO Miao;CHEN Keyan;REN Lu;QI Jing;CHEN Chen;LIU Zhuang;HOU Ping(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;China Medical University,Shenyang 110001,Liaoning,China;The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]中国医科大学,辽宁沈阳110001 [3]辽宁中医药大学附属医院,辽宁沈阳110032

出　　处：《中华中医药学刊》2023年第2期39-43,I0013,I0014,共7页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81874403);辽宁省“兴辽英才”人才项目(XLYC1802099);辽宁省特聘教授项目(辽教发[2015]153号)。

摘　　要：目的研究参仙升脉口服液对病态窦房结综合征(sick sinus syndrome,SSS)小鼠认知功能的干预作用及效应机制。方法15只C57BL/6小鼠分为假手术组、模型组及治疗组,每组5只。采用皮下微量渗透泵入AngⅡ的方法建立SSS模型,治疗组于造模后第2天给予参仙升脉口服液5 mL/(kg·d)灌胃治疗,假手术组及模型组给予等量氯化钠溶液灌胃。28 d后检测各组小鼠心率及脑血流量,行为学实验评价小鼠学习记忆能力,HE染色观察脑组织病理改变,TUNEL染色检测神经元凋亡,DHE染色检测脑组织活性氧(reactive oxygen species,ROS)含量,Western blot法测定脑组织环磷酸腺苷(cyclic adenosine monophosphate,cAMP)、cAMP应答元件结合蛋白(cAMP-response element binding protein,CREB)、磷酸化的CREB(phosphorylated CREB,p-CREB)、促过氧化物酶体增生物激活受体γ辅激活因子-1α(peroxisome proliferator-activated receptorγcoactivator-1α,PGC-1α)蛋白的表达。结果与假手术组相比,模型组小鼠心率显著下降(P<0.05),学习记忆能力下降(P<0.01,P<0.05),脑血流量降低(P<0.05),脑组织出现病理损伤,神经元凋亡增加,ROS积聚明显(P<0.01),cAMP、CREB、p-CREB、PGC-1α蛋白的表达降低(P<0.01)。与模型组相比,治疗组小鼠心率下降得到显著抑制(P<0.05),学习能力改善(P<0.05),神经元凋亡及ROS聚集明显减轻(P<0.01),cAMP、CREB、p-CREB、PGC-1α蛋白的表达均升高(P<0.05)。结论参仙升脉口服液不仅提升AngⅡ诱导的SSS模型小鼠心率,而且可能通过调控cAMP/CREB/PGC-1α通路改善认知功能,起到非心率依赖性的脑保护作用。Objective To investigate the intervention effects and effector mechanisms of Shenxian Shengmai Oral Liquid(参仙升脉口服液)on cognitive function in mice with sick sinus syndrome.Methods Fifteen C57BL/6 mice were divided into the sham surgery group(SHAM),model group(SSS)and treatment group(SXSM).There were five mice in each group.A subcuta⁃neous micro-osmotic pump was used to inject AngII to simulate SSS.The next day after modeling,SXSM group was given Shenxian Shengmai Oral Liquid 5 mL/(kg·d)by gavage,and the same amount of normal saline was given by gavage in SHAM group and SSS group.After 28 days,the heart rate and cerebral blood flow of the mice in each group were detected.Behavioral experiments were performed to evaluate the learning and memory ability of the mice.The pathological changes of the brain tissues were observed by HE staining.Neuronal apoptosis was assessed by TUNEL staining,reactive oxygen species(ROS)by DHE stai⁃ning,and the protein expressions of cyclic adenosine monophosphate(cAMP),cAMP-response element binding protein(CREB),phosphorylated CREB(p-CREB)and peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α)in brain tissues were determined by Western blot analysis.Results Compared with the SHAM group,the mice in the SSS group had a significant decrease in heart rate(P<0.05),lower learning and memory ability(P<0.01,P<0.05),lower cerebral blood flow(P<0.05),pathological damage to the brain tissue,increased neuronal apoptosis and significant accumulation of ROS(P<0.01),reduced protein expressions of the cAMP,CREB,p-CREB and PGC-1α(P<0.01).Compared with SSS group,SXSM group significantly inhibited the decrease of heart rate(P<0.05),improved learning ability(P<0.05)and significantly reduced neuronal apoptosis and ROS aggregation(P<0.01).The protein expressions of cAMP,CREB,p-CREB and PGC-1αelevated in the SXSM group(P<0.05).Conclusion SXSM elevates the heart rate in AngII induced SSS model mice.At the same time,SXSM possibly improves the cognitive function through the cA

关 键 词：病态窦房结综合征 认知功能 参仙升脉口服液 cAMP/CREB/PGC-1α 氧化应激 

分 类 号：R285.5[医药卫生—中药学]