摘要
目的探讨电针对自发性高血压大鼠血压昼夜节律、心脏时钟基因及代谢物的影响,及其改善昼夜节律紊乱的机制。方法选取19周龄SPF级雄性自发性高血压大鼠24只,采用随机数字表法将其分为模型组、电针组、假电针组和西药组,每组6只;另选6只WKY大鼠作为对照组。所有大鼠予以异氟烷气体麻醉和抓取固定;电针组取双侧内关穴、厥阴俞穴行电针干预,每次15 min;假电针组在相同穴位旁5 mm处浅刺不通电;西药组灌胃缬沙坦7.2 mg/(kg·次),各组均干预6周。检测各组大鼠血压水平、血压昼夜节律变化;RT-qPCR观察各组大鼠心脏Bmal1、Clock、Rev-erbα、Per1/2、Cry1/2 mRNA表达;代谢组学技术检测大鼠心脏代谢产物水平;Spearman评估时钟基因与差异代谢物的相关性。结果与对照组比较,模型组大鼠昼间和夜间收缩压、平均动脉压和舒张压升高(P<0.05);与假电针组比较,电针组昼间和夜间收缩压,昼间平均动脉压和夜间舒张压降低(P<0.05)。与对照组比较,模型组收缩压谷、峰值及中值升高,杓型率、振幅降低(P<0.05)。与假电针组比较,电针组收缩压谷、峰值及中值降低,杓型率、振幅升高(P<0.05)。与对照组比较,模型组Bmal1、Per2、Rev-erbαmRNA表达降低,Clock、Per1、Cry1、Cry2 mRNA表达升高(P<0.05)。与假电针组比较,电针组Bmal1、Per2 mRNA表达升高,Per1、Cry1、Cry2 mRNA表达降低(P<0.05)。对照组与模型组共有134个差异代谢物(79个上调,55个下调);电针组与模型组共有92个差异代谢物(66个上调,26个下调),三组间共有9个关键差异代谢物。电针组与模型组相关性较高的通路有磷酸戊糖途径及不饱和脂肪酸合成途径。时钟基因(Bmal1、Per1/2、Cry1/2)与辅酶Q2、二十二五碳烯酸、D-赤藓糖-4-磷酸具有相关性(P<0.05)。结论电针可改善自发性高血压大鼠血压昼夜节律紊乱,其作用可能通过调控心脏时钟基因与关键代谢物之间的相互作用,涉及磷酸戊糖和不饱和脂肪酸代谢调节,恢复昼夜节律稳态。
Objective To explore the effect of electroacupuncture on blood pressure circadian rhythm,cardiac clock genes and metabolites in spontaneously hypertensive rats,as well as the mechanism by which it improves circadian rhythm disorders.Methods Twenty-four 19-week-old SPF-grade male spontaneously hypertensive rats were selected and were divided into model group,electroacupuncture group,sham electroacupuncture group,and western medicine group by random number table method,with 6 rats in each group;another 6 WKY rats were selected as the control group.All rats were anesthetized with Isoflurane gas and fixed by grasping;in the electroacupuncture group,electroacupuncture was performed on both nèiguān and juéyīnshùpoints for 15 minutes each time;the sham electroacupuncture group made a shallow puncture 5 mm away from the same acupoint without applying electricity;and the western medicine group was administered Valsartan at a dose of 7.2 mg/(kg·time)by gavage,and each group was intervened for six weeks.The blood pressure levels and blood pressure circadian rhythm changes in each group of rats were detected;the mRNA expressions of cardiac Bmal1,Clock,Rev-erbα,Per1/2,and Cry1/2 of rats in each group were observed by RT-qPCR;metabolomics technology was used to detect the levels of cardiac metabolites in rats;and Spearman was used to evaluate the correlation between clock genes and differential metabolites.Results Compared with the control group,the daytime and nighttime systolic blood pressure,mean arterial pressure,and diastolic blood pressure of rats in the model group increased(P<0.05);compared with the sham electroacupuncture group,the daytime and nighttime systolic blood pressure,the daytime mean arterial blood pressure,and the nighttime diastolic blood pressure in the electroacupuncture group were decreased(P<0.05).Compared with the control group,the trough,peak,and median of systolic blood pressure in the model group increased,while the ladder-shaped rate and amplitude decreased(P<0.05).Compared with the sham electroacupuncture group,the trough,peak,and median of systolic blood pressure in the electroacupuncture group decreased,while the dipper rate and amplitude increased(P<0.05).Compared with the control group,the expressions of Bmal1,Per2,and Rev-erbαmRNA in the model group decreased,while the expressions of Clock,Per1,Cry1,and Cry2 mRNA increased(P<0.05).Compared with the sham electroacupuncture group,the expressions of Bmal1 and Per2 mRNA in the electroacupuncture group increased,while the mRNA expressions of Per1,Cry1 and Cry2 mRNA decreased(P<0.05).There were 134 differential metabolites(79 up-regulated and 55 down-regulated)between the control group and the model group;there were 92 differential metabolites(66 up-regulated and 26 down-regulated)between the electroacupuncture group and the model group,and there were nine key differential metabolites among the three groups.The pathways with a relatively high correlation between the electroacupuncture group and the model group include the pentose phosphate pathway and the unsaturated fatty acid synthesis pathway.The clock genes(Bmal1,Per1/2,Cry1/2)were correlated with coenzyme Q2,oxalic acid and D-erythrito-4-phosphate(P<0.05).Conclusion Electroacupuncture can improve the blood pressure circadian rhythm disorder in spontaneously hypertensive rats.Its effect may be achieved by regulating the interaction between cardiac clock genes and key metabolites,involving the pentose phosphate and the regulation of unsaturated fatty acid metabolism,to restore the homeostasis of the circadian rhythm.
作者
张聪
陈溢滢
张贝
胡雯馨
解瑞梓
李佳芹
陈理
ZHANG Cong;CHEN Yiying;ZHANG Bei;HU Wenxin;XIE Ruizi;LI Jiaqin;CHEN Li(Department of Acupuncture Rehabilitation,Affiliated Hospital of Nanjing University of Chinese Medicine,Jiangsu Province,Nanjing 210029,China)
出处
《中国医药导报》
2026年第7期29-37,44,共10页
China Medical Herald
基金
江苏省科技计划专项资金(重点研发计划社会发展)项目(BE2023794)
江苏省中医院科主任学术提升专项课题(Y2022ZR31)
江苏省研究生科研与实践创新计划项目(KYCX23_2010)。
关键词
高血压
电针
血压昼夜节律
代谢组学
时钟基因
Hypertension
Electroacupuncture
Blood pressure circadian rhythm
Metabolomics
Clock genes
