动脉压力感受性反射ABR功能与脑卒中.ppt

ABR功能与脑卒中,Ding-Feng Su 苏定冯,Shanghai,China,脑卒中的严重性,脑卒中俗称“中风”，是高血压病最严重的并发症之一；全世界每年有1500万新发生脑卒中的病人；我国有1.6亿高血压病人，我国脑卒中的发病率明显高于欧美国家；卫生部5月9日公布，城市人口死因：肿瘤、脑血管病、心脏病；农村人口死因：肿瘤、脑血管病、呼吸系统疾病。,脑卒中的严重性,脑卒中一旦发生，病人非死即残。不但死亡率高，而且治疗困难，想让病人完全康复更加困难。因此脑卒中的预防非常重要。,脑卒中预防的必要性,现有的措施：降压、运动、戒烟，等。全世界每年仍然有1500万新发生脑卒中的病人，说明问题没有解决。因此，开展基础研究，找出决定脑卒中发生与否的重要因素，探讨脑卒中预防的新策略是非常必要的。,Arterial baroreflex(ABR),Baroreflex Sensitivity(BRS),一、ABR功能与脑卒中的发生,动脉压力感受性反射,Stroke-Prone spontaneously hypertensive rats(SHR-SP）,infarction,hemorrhage,Male:9 M;Female:13 M,BRS is an important determinant for stroke,BRS0.3,BRS0.3,proportion surviving,Sinoaortic denervation(SAD),SAD:sinoaortic denervation,SAD on the hemodynamic and cerebral ischemia,偶联皂草素的P物质(SP-SAP),SP-SAP,SP-SAP on the hemodynamic and cerebral ischemia,hemodynamic and cerebral ischemia in rats with lower BRS,二、ABR介导热量限制的保护作用,热量限制 延长寿命 热门话题 CNS 低等生物SHR-SP 寿命与脑卒中3月龄 正常食料的60%,Effects of CR on survival time in SHR-SP,proportion surviving,Log-Rank 67.68 P.0001,AL,CR,Age(days),At age of 12 months,Means of survival time(weeks),Effects of CR on BP&BRS,Effects of CR on serum lipids,Effects of CR on apoptosis of neural and myocardial cells,AL CR,Myocardial cells,Neural cells,Sir2-like proteins(sirtuins)are a family of NAD+-depandent deacetylases.,It is accepted that the effects of CR on lifespan is mediated by the activation of sirtuins.,Sirtuins,Effects of CR on sirtuin,AL CR AL CR AL CR,ABR function and Situin,gene,protein,Sirt1-actin,Heart Kidney,ABR dysfunction prevented the activation of sirtuin by CR,Sirt1-actin,Brain,heart,Sirt1-actin,Kidney,Sirt1-actin,proportion surviving,proportion surviving,Age(days),AL,AL,CR,CR,三、ABR功能影响脑卒中的机制,工作假设：,ABR功能迷走神经功能内源性递质ACh尼古丁a7功能炎症反应促进脑卒中发生,Sham,SAD,SAD导致疑核基础电活动减弱,SAD导致心脏迷走神经张力降低,SAD导致心脏迷走神经张力降低,反射功能缺陷与a7炎性通路,AchTactin,7actin,7actin,AchTactin,Sham SAD,AchTactin,Sham SAD,CR和SAD对炎性因子表达的影响,四、脑卒中防治的新策略,Ketanserin（酮色林）An antagonist for 5-HT2A receptor with minor effect on blocking a1 receptor;Enhancing BRS in SHR with a small dose;Acting site:RVLM,but not NTS.,Effects of ket on SBP(a single dose,ig),Effects of ket on BRS(a single dose,ig),Effects of long-term treatment with Ket on BP&BRS,Time(days),proportion surviving,Control,0.3mg/kg,3.0mg/kg,Log-Rank 59.13P0.0001,Effects of lifelong treatment with Ket on survival time in SHR-SP,Thank you,