三七总皂苷对氯化钙-乙酰胆碱诱导大鼠房颤的干预效应机制
|
摘要
目的:通过复制氯化钙-乙酰胆碱(CaCl_2-ACh)诱导的大鼠房颤模型,观察并研究三七总皂苷(PNS)对房颤的干预作用及相关机制,以期为基于三七总皂苷的房颤治疗药物的临床应用与治疗方案优化提供科学的实验和理论依据。方法:将SD雄性大鼠随机分为正常组、模型组、PNS低剂量组、PNS高剂量组,模型组和PNS低、高剂量组接受CaCl_2-ACh尾静脉注射进行房颤模型制备,在此基础上,各PNS治疗组腹腔注射PNS进行干预,正常组和模型组腹腔注射0.9%氯化钠溶液作为对照。PNS连续治疗11d后进行后续的分析。尾静脉造模给药和PNS治疗给药后30min,采用10%水合氯醛(3mL/kg)腹腔注射进行麻醉后进行体表心电图监测,光镜下观察大鼠心肌形态学改变以及胶原沉积;大鼠心肌组织进行总RNA抽提及逆转录后,采用荧光实时定量PCR分析心肌组织胶原及细胞外基质形成相关基因(Col1a1、Col1a2、Col3a1、Col5a2、Timp1及Fbn1)的mRNA表达水平;分离大鼠血清后,检测大鼠血清IL-8、IL-10、IL-17A、IFN-γ、ROS、MDA、AOPP及SOD等炎症相关细胞因子及氧化应激标志物的水平。结果:与模型组比较,PNS能显著降低房颤及期前收缩发生率及心肌组织损伤(P<0.05),显著降低血清中氧化应激标志物与炎症因子水平(P<0.05),显著降低心肌胶原沉积(P<0.05)。结论:PNS能有效的减轻房颤,其抗房颤的效应可能与减轻心肌组织损伤、减轻机体炎症与氧化应激作用相关。
Objective: To investigate the anti-fibrillation effect and mechanisms of panax notoginseng saponins(PNS)in the rat model of CaCl_2-ACh-induced atrial fibrillation, and to provide reliable experimental and scientific evidence for the development of PNS-based therapies that may help to further optimize the current treatment of atrial fibrillation. Methods: SD male rats were randomly divided into normal group, model group, PNS low-dose treatment group and PNS high-dose treatment group. Model group, PNS low-and high-dose treatment groups received CaCl_2-ACh tail vein injection for atrial fibrillation model preparation. On this basis, each PNS treatment group was intraperitoneally injected with PNS for intervention. The normal control group and the model group were intraperitoneally injected with 0.9% normal saline as a control. Subsequent analysis was performed after 11 days continuous treatment with PNS. Thirty minutes after administration of tail vein modeling and PNS treatment, 10% chloralhydrate(3 mL/kg bw) was intraperitoneally injected, followed by body surface ECG measurement for 30 min. H&E staining and Masson's trichrome staining were performed to examine the gross morphological changes and collagen deposition of the heart collected from rats at the end of the experiment. Total RNA was isolated, reverse-transcribed and real-time PCR analyses were performed to examine the expression of Col1 a1, Col1 a2, Col3 a1, Col5 a2, Timp1 and Fbn1. Enzyme-linked immunosorbent assay was performed to analyze the serum levels of inflammatory factors IL-8, IL-10, IL-17 A, IFN-γ and markers of oxidative stress ROS, MDA, AOPP and SOD. Results: Compared with the model group, PNS could significantly reduce the incidence of atrial fibrillation and pre-systolic and myocardial injury(P<0.05), and PNS significantly reduce serum levels of oxidative stress markers and inflammatory factors(P<0.05), and it significantly reduced myocardial collagen deposition(P<0.05).Conclusion: PNS can effectively attenuate atrial fibrillation, and its anti-atrial fibrillation effect may be related to the reduction of myocardial tissue damage, reduction of body inflammation and oxidative stress.
Objective: To investigate the anti-fibrillation effect and mechanisms of panax notoginseng saponins(PNS)in the rat model of CaCl_2-ACh-induced atrial fibrillation, and to provide reliable experimental and scientific evidence for the development of PNS-based therapies that may help to further optimize the current treatment of atrial fibrillation. Methods: SD male rats were randomly divided into normal group, model group, PNS low-dose treatment group and PNS high-dose treatment group. Model group, PNS low-and high-dose treatment groups received CaCl_2-ACh tail vein injection for atrial fibrillation model preparation. On this basis, each PNS treatment group was intraperitoneally injected with PNS for intervention. The normal control group and the model group were intraperitoneally injected with 0.9% normal saline as a control. Subsequent analysis was performed after 11 days continuous treatment with PNS. Thirty minutes after administration of tail vein modeling and PNS treatment, 10% chloralhydrate(3 mL/kg bw) was intraperitoneally injected, followed by body surface ECG measurement for 30 min. H&E staining and Masson's trichrome staining were performed to examine the gross morphological changes and collagen deposition of the heart collected from rats at the end of the experiment. Total RNA was isolated, reverse-transcribed and real-time PCR analyses were performed to examine the expression of Col1 a1, Col1 a2, Col3 a1, Col5 a2, Timp1 and Fbn1. Enzyme-linked immunosorbent assay was performed to analyze the serum levels of inflammatory factors IL-8, IL-10, IL-17 A, IFN-γ and markers of oxidative stress ROS, MDA, AOPP and SOD. Results: Compared with the model group, PNS could significantly reduce the incidence of atrial fibrillation and pre-systolic and myocardial injury(P<0.05), and PNS significantly reduce serum levels of oxidative stress markers and inflammatory factors(P<0.05), and it significantly reduced myocardial collagen deposition(P<0.05).Conclusion: PNS can effectively attenuate atrial fibrillation, and its anti-atrial fibrillation effect may be related to the reduction of myocardial tissue damage, reduction of body inflammation and oxidative stress.
引文
[1]Kallistratos M S.Atrial fibrillation and arterial hypertension.Pharmacol Res,2018,28:322-326
[2]Bai Q,Yan H,Sheng Y,et al.Long-term acetaminophen treatment induced liver fibrosis in mice and the involvement of Egr-1.Toxicology,2017,382:145-162
[3]Wipff J,Allanore Y,Boileau C.Interactions between fibrillin-1 and tgf-beta:Consequences and human pathology.Medecine Sciences,2009,25(2):161-167
[4]Hwang H J,Ha J W,Joung B,et al.Relation of inflammation and left atrial remodeling in atrial fibrillation occurring in early phase of acute myocardial infarction.International Journal of Cardiology,2011,146(1):28-31
[5]da Silva R M.Influence of Inflammation and Atherosclerosis in Atrial Fibrillation.Current Atherosclerosis Reports,2017,19(1):2-8
[6]Ishii Y,Schuessler R B,Gaynor S L,et al.Postoperative atrial fibrillation:The role of the inflammatory response.The Journal of Thoracic and Cardiovascular Surgery,2017,144(2):211-235
[7]Cheng T,Wang X F,Hou Y T,et al.Correlation between atrial fibrillation,serum amyloid protein A and other inflammatory cytokines.Molecular Medicine Reports,2012,6(3):581-584
[8]Beringer A,Noack M,Miossec P.IL-17 in Chronic Inflammation:From Discovery to Targeting.Trends in Molecular Medicine,2016,22(3):230-241
[9]Bullens D M,Truyen E,Coteur L,et al.IL-17 mRNA in sputum of asthmatic patients:Linking T cell driven inflammation and granulocytic influx?Respiratory Research,2006,7:135
[10]Wang Z,Lee J,Zhang Y,et al.Increased Th17 cells in coronary artery disease are associated with neutrophilic inflammation.Scandinavian Cardiovascular Journal,2011,45(1):54-61
[11]Fu X X,Zhao N,Dong Q,et al.Interleukin-17A contributes to the development of post-operative atrial fibrillation by regulating inflammation and fibrosis in rats with sterile pericarditis.International Journal of Molecular Medicine,2015,36(1):83-92
[12]Sun Q,Wei W,Sha W.Potential Role for Mycobacterium tuberculosis Specific IL-2 and IFN-gamma Responses in Discriminating between Latent Infection and Active Disease after Long-Term Stimulation.PloS one,2016,11(12):e0166501
[13]Hansson G K,Jonasson L,Holm J,et al.Gamma-interferon regulates vascular smooth muscle proliferation and Ia antigen expression in vivo and in vitro.Circulation Research,1988,63(4):712-719
[14]Morry J,Ngamcherdtrakul W,Yantasee W.Oxidative stress in cancer and fibrosis:Opportunity for therapeutic intervention with antioxidant compounds,enzymes,and nanoparticles.Redox Biology,2016,11:240-253
[15]Brandes R P,Weissmann N,Schroder K.Nox family NADPH oxidases:Molecular mechanisms of activation.Free Radical Biology&Medicine,2014,76:208-226
[16]Depre C,Kim S J,John A S,et al.Program of cell survival underlying human and experimental hibernating myocardium.Circulation Research,2004,95(4):433-440
[2]Bai Q,Yan H,Sheng Y,et al.Long-term acetaminophen treatment induced liver fibrosis in mice and the involvement of Egr-1.Toxicology,2017,382:145-162
[3]Wipff J,Allanore Y,Boileau C.Interactions between fibrillin-1 and tgf-beta:Consequences and human pathology.Medecine Sciences,2009,25(2):161-167
[4]Hwang H J,Ha J W,Joung B,et al.Relation of inflammation and left atrial remodeling in atrial fibrillation occurring in early phase of acute myocardial infarction.International Journal of Cardiology,2011,146(1):28-31
[5]da Silva R M.Influence of Inflammation and Atherosclerosis in Atrial Fibrillation.Current Atherosclerosis Reports,2017,19(1):2-8
[6]Ishii Y,Schuessler R B,Gaynor S L,et al.Postoperative atrial fibrillation:The role of the inflammatory response.The Journal of Thoracic and Cardiovascular Surgery,2017,144(2):211-235
[7]Cheng T,Wang X F,Hou Y T,et al.Correlation between atrial fibrillation,serum amyloid protein A and other inflammatory cytokines.Molecular Medicine Reports,2012,6(3):581-584
[8]Beringer A,Noack M,Miossec P.IL-17 in Chronic Inflammation:From Discovery to Targeting.Trends in Molecular Medicine,2016,22(3):230-241
[9]Bullens D M,Truyen E,Coteur L,et al.IL-17 mRNA in sputum of asthmatic patients:Linking T cell driven inflammation and granulocytic influx?Respiratory Research,2006,7:135
[10]Wang Z,Lee J,Zhang Y,et al.Increased Th17 cells in coronary artery disease are associated with neutrophilic inflammation.Scandinavian Cardiovascular Journal,2011,45(1):54-61
[11]Fu X X,Zhao N,Dong Q,et al.Interleukin-17A contributes to the development of post-operative atrial fibrillation by regulating inflammation and fibrosis in rats with sterile pericarditis.International Journal of Molecular Medicine,2015,36(1):83-92
[12]Sun Q,Wei W,Sha W.Potential Role for Mycobacterium tuberculosis Specific IL-2 and IFN-gamma Responses in Discriminating between Latent Infection and Active Disease after Long-Term Stimulation.PloS one,2016,11(12):e0166501
[13]Hansson G K,Jonasson L,Holm J,et al.Gamma-interferon regulates vascular smooth muscle proliferation and Ia antigen expression in vivo and in vitro.Circulation Research,1988,63(4):712-719
[14]Morry J,Ngamcherdtrakul W,Yantasee W.Oxidative stress in cancer and fibrosis:Opportunity for therapeutic intervention with antioxidant compounds,enzymes,and nanoparticles.Redox Biology,2016,11:240-253
[15]Brandes R P,Weissmann N,Schroder K.Nox family NADPH oxidases:Molecular mechanisms of activation.Free Radical Biology&Medicine,2014,76:208-226
[16]Depre C,Kim S J,John A S,et al.Program of cell survival underlying human and experimental hibernating myocardium.Circulation Research,2004,95(4):433-440
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |