Objective： To observe abnormalities in heart rate variability （HRV） in diabetic rats and to explore the effects of treatment with Guizhi Decoction （桂枝汤） on cardiac autonomic nervous （CAN） imbalance. Methods...Objective： To observe abnormalities in heart rate variability （HRV） in diabetic rats and to explore the effects of treatment with Guizhi Decoction （桂枝汤） on cardiac autonomic nervous （CAN） imbalance. Methods： A radio-telemetry system for monitoring physiological parameters was implanted into rats to record electrocardiac signals and all indictors of HRV [time domain measures： standard deviation of all RR intervals in 24 h （SDNN）, root mean square of successive differences （RMSSD）, percentage of differences between adjacent RR intervals greater than 50 ms （PNN50）, and standard deviation of the averages of RR intervals （SDANN）; frequency domain measures： low frequency （LF）, high frequency （HF）, total power （TP）, and LF/HF ratio]. The normal group was randomly selected, and the remaining rats were used to establish streptozocin （STZ）-induced diabetic model. After 4 weeks, the model rats were divided into the model group, the methycobal group, and the Guizhi Decoction group, 9 rats in each group. Four weeks after intragastric administration of the corresponding drugs, the right atria of the rats were collected for immunohistochemical staining of tyrosine hydroxylase （TH） and choline acetyltransferase （CHAT） to observe the distribution of the sympathetic and vagus nerves in the right atrium. The myocardial homogenate from the interventricular septum and the left ventricle was used for determination of TH, CHAT, growth-associated protein 43 （GAP-43）, nerve growth factor （NGF）, and ciliary neurotrophic factor （CNTF） levels using an enzyme-linked immunosorbent assay. Results： （1） STZ rats had elevated blood glucose levels, reduced body weight, and decreased heart rate; there was no difference between the model group and the drug treated groups. （2） Compared with the model group, only RMSSD and TP increased in the methycobal group significantly （P〈0.05）; SDNN, RMSSD, PNN50, LF, HF, and TP increased, LF/HF decreased （P〈0.05）,展开更多
前期已证实红花-葶苈子药对作用于成纤维细胞抑制心肌纤维化,该研究则联合网络药理学和实验验证进一步探究红花-葶苈子药对通过改善心脏微环境抑制心肌纤维化的可能机制。通过检索中药系统药理学数据库与分析平台(Traditional Chinese M...前期已证实红花-葶苈子药对作用于成纤维细胞抑制心肌纤维化,该研究则联合网络药理学和实验验证进一步探究红花-葶苈子药对通过改善心脏微环境抑制心肌纤维化的可能机制。通过检索中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)筛选红花-葶苈子药对活性成分及靶点,GeneCards、药物遗传学与药物基因组学知识库(Pharmacogenetics and Pharmacogenomics Knowledge Base,PharmGKB)、在线孟德尔人类遗传数据库(Online Mendelian Inheritance in Man,OMIM)等数据库获取心肌纤维化靶点,运用Cytoscape 3.8.1软件绘制"活性成分-靶点-疾病"网络。采用STRING数据库构建靶点相互作用网络,CluoGo插件进行生物过程分析,联合使用京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)和Funrich数据库进行通路富集分析。构建血管紧张素Ⅱ诱导心肌纤维化大鼠,观察红花-葶苈子药对抑制心肌纤维化疗效;选取网络药理学预测与血管内皮细胞相关的信号通路,RT-PCR、ELISA验证红花-葶苈子药对对其相关靶标的影响。结果共筛选出红花-葶苈子药对活性成分31个及相应靶点204个,心肌纤维化靶点4 671个,交集靶点174个。红花-葶苈子药对治疗心肌纤维化的关键靶点包括RAC-α丝氨酸/苏氨酸蛋白激酶(RAC-alpha serine/threonine-protein kinase,AKT1)、转录因子激活蛋白-1 (transcription factor AP-1,JUN)、丝裂原激活的蛋白激酶1 (mitogen-activated protein kinase 1,MAPK1)、p53蛋白(cellular tumor antigen p53,TP53)、转录因子p65 (transcription factor p65,RELA)、丝裂原激活的蛋白激酶8 (mitogen-activated protein kinase 8,MAPK8)等,生物过程涉及血管直径调节、血管内皮细胞迁移调节、氧化应激引起的细胞死亡等。通路富集分析涉及晚期糖基化产物(advanced glycation end products,AGE)-晚期糖基化终末产物受体(receptor展开更多
基金Supported by the National Natural Science Foundation of China(No.81072962)the Special Fund of Taishan Scholars Program of Shandong Province(No.2012-55)
文摘Objective： To observe abnormalities in heart rate variability （HRV） in diabetic rats and to explore the effects of treatment with Guizhi Decoction （桂枝汤） on cardiac autonomic nervous （CAN） imbalance. Methods： A radio-telemetry system for monitoring physiological parameters was implanted into rats to record electrocardiac signals and all indictors of HRV [time domain measures： standard deviation of all RR intervals in 24 h （SDNN）, root mean square of successive differences （RMSSD）, percentage of differences between adjacent RR intervals greater than 50 ms （PNN50）, and standard deviation of the averages of RR intervals （SDANN）; frequency domain measures： low frequency （LF）, high frequency （HF）, total power （TP）, and LF/HF ratio]. The normal group was randomly selected, and the remaining rats were used to establish streptozocin （STZ）-induced diabetic model. After 4 weeks, the model rats were divided into the model group, the methycobal group, and the Guizhi Decoction group, 9 rats in each group. Four weeks after intragastric administration of the corresponding drugs, the right atria of the rats were collected for immunohistochemical staining of tyrosine hydroxylase （TH） and choline acetyltransferase （CHAT） to observe the distribution of the sympathetic and vagus nerves in the right atrium. The myocardial homogenate from the interventricular septum and the left ventricle was used for determination of TH, CHAT, growth-associated protein 43 （GAP-43）, nerve growth factor （NGF）, and ciliary neurotrophic factor （CNTF） levels using an enzyme-linked immunosorbent assay. Results： （1） STZ rats had elevated blood glucose levels, reduced body weight, and decreased heart rate; there was no difference between the model group and the drug treated groups. （2） Compared with the model group, only RMSSD and TP increased in the methycobal group significantly （P〈0.05）; SDNN, RMSSD, PNN50, LF, HF, and TP increased, LF/HF decreased （P〈0.05）,
文摘前期已证实红花-葶苈子药对作用于成纤维细胞抑制心肌纤维化,该研究则联合网络药理学和实验验证进一步探究红花-葶苈子药对通过改善心脏微环境抑制心肌纤维化的可能机制。通过检索中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)筛选红花-葶苈子药对活性成分及靶点,GeneCards、药物遗传学与药物基因组学知识库(Pharmacogenetics and Pharmacogenomics Knowledge Base,PharmGKB)、在线孟德尔人类遗传数据库(Online Mendelian Inheritance in Man,OMIM)等数据库获取心肌纤维化靶点,运用Cytoscape 3.8.1软件绘制"活性成分-靶点-疾病"网络。采用STRING数据库构建靶点相互作用网络,CluoGo插件进行生物过程分析,联合使用京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)和Funrich数据库进行通路富集分析。构建血管紧张素Ⅱ诱导心肌纤维化大鼠,观察红花-葶苈子药对抑制心肌纤维化疗效;选取网络药理学预测与血管内皮细胞相关的信号通路,RT-PCR、ELISA验证红花-葶苈子药对对其相关靶标的影响。结果共筛选出红花-葶苈子药对活性成分31个及相应靶点204个,心肌纤维化靶点4 671个,交集靶点174个。红花-葶苈子药对治疗心肌纤维化的关键靶点包括RAC-α丝氨酸/苏氨酸蛋白激酶(RAC-alpha serine/threonine-protein kinase,AKT1)、转录因子激活蛋白-1 (transcription factor AP-1,JUN)、丝裂原激活的蛋白激酶1 (mitogen-activated protein kinase 1,MAPK1)、p53蛋白(cellular tumor antigen p53,TP53)、转录因子p65 (transcription factor p65,RELA)、丝裂原激活的蛋白激酶8 (mitogen-activated protein kinase 8,MAPK8)等,生物过程涉及血管直径调节、血管内皮细胞迁移调节、氧化应激引起的细胞死亡等。通路富集分析涉及晚期糖基化产物(advanced glycation end products,AGE)-晚期糖基化终末产物受体(receptor
