| 摘要: |
| 目的:探讨氯沙坦(losartan)对自发性高血压大鼠(spontaneously hypertensive rat,SHR)急性脑梗死保护作用的动脉压力感受性反射(arterial baroreflex,ABR)机制。方法:灌胃给予氯沙坦2周,测定大鼠血流动力学指标及BRS (ABR功能用动脉压力感受性反射敏感性,baroreflex sensitivity)值。采用大脑中动脉 (middle cerebral arterial,MCA) 栓塞的方法诱发急性脑梗死,24 h后取脑组织,切片、染色,观察急性脑梗死面积;孤束核(nucleus of solitary tract,NTS)分别微量注射血管紧张素Ⅱ(angiotensionⅡ,AngⅡ)及小剂量氯沙坦,测定大鼠血流动力学指标及BRS值,采用MCA栓塞的方法诱发急性脑梗死,观察药物对急性脑梗死的影响。结果:与对照组相比,灌胃给予氯沙坦后大鼠ABR功能改善,脑梗死面积显著降低(P<0.05)。孤束核微量注射AngⅡ可明显升高动物血压,降低BRS值;孤束核微量注射氯沙坦后在不改变血压的情况下可以使ABR功能明显改善(P<0.05),减轻脑梗死损伤(P<0.05)。结论:氯沙坦改善了ABR的敏感性,从而对急性脑梗死起防治作用,孤束核可能是其作用部位。 |
| 关键词: 近交SHR大鼠；脑梗死；氯沙坦 血管紧张素Ⅱ 孤束核 动脉压力感受性反射 |
| DOI：10.3724/SP.J.1008.2009.01126 |
| 投稿时间：2009-01-14修订日期：2009-03-19 |
| 基金项目:国家重点基础研究发展计划(“973”计划，2009CB521901),国家自然科学基金 (30500614). |
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| Losartan alleviates acute cerebral ischemia in spontaneously hypertensive rats:the arterial baroreflex function |
| WU Jian,ZHOU Rui-rui,GUO Jin-min,CAI Guo-jun,LIU Ai-jun*,SU Ding-feng* |
| (Department of Pharmacology,School of Pharmacy,Second Military Medical University,Shanghai 200433,China) |
| Abstract: |
| Objective:To investigate the arterial baroreflex (ABR)-associated mechanism of losartan in protection of acute cerebral ischemia injury in spontaneously hypertensive rats (SHRs).Methods:Losartan (10 mg·kg-1·d-1) were administered i.g. to SHRs for 2 weeks,and the hemodynamic parameters and the baroreflex sensitivity (BRS) was determined.Then the rats were subjected to middle cerebral arterial (MCA) occlusion to establish acute cerebreal ischemia.The brain samples were obtained,sectioned and stained 24 h later; the infarction area of the brain was measured.Losartan and angiotensinⅡ (AngⅡ,100 pmol) were also microinjected into the nucleus of solitary tract (NTS) of rats,and the hemodynamic parameters and BRS were determined 24 h later.Then the rats were subjected to MCA occlusion to establish acute cerebral ischemia injury.The brain infarction area was measured 24 h after operation.Results:Compared to control rats,intragastric administration of losartan improved the ABR function and significantly decreased the infarction area (P<0.05).NTS microinjection of AngⅡ obviously increased the blood pressure,and decreased BRS value of rats.NTS microinjection of losartan did not change the blood pressure,and significantly improved the ABR function(P<0.05) and alleviated cerebral infarction injury(P<0.05).Conclusion:Losartan can improve the sensitivity of ABR and prevent acute cerebral infarction; NTS might be the target of losartan. |
| Key words: inbred SHR rats brain infarction losartan angiotensinⅡ nucleus of solitary tract arterial baroreflex |
