波生坦对DOCA-盐型高血压大鼠肾脏的保护作用  

Renoprotective Effects of Bosentan on DOCA-salt Hypertensive Rats

作　　者：王凯旋[1] 洪小苏[1] 陈建昌[1] 高岚[1] 焦阳[1] 谢芳[2] 

机构地区：[1]苏州大学附属第二医院心内科,苏州215004 [2]苏州大学医学院病理学教研室,苏州215007

出　　处：《中国血液流变学杂志》2004年第3期301-304,共4页Chinese Journal of Hemorheology

摘　　要：目的　观察内皮素受体阻断剂波生坦 (bosentan)对DOCA 盐型高血压大鼠 (DHR)的肾脏保护作用。方法　采用 10周龄雄性SD大鼠 ,切除左侧肾脏 ,术后予抗感染 ,1周后存活大鼠随机分成 4组。对照组给予饮自来水。其他组予DOCA皮下注射 ,饮盐水。其中 2组分别给予波生坦及氨氯地平 ,安慰剂组给予等量自来水灌胃共 5周。留取血、尿送生化检测 ;摘取肾脏 ,石蜡包埋卮作组织学和免疫组化检测。结果　与对照组相比 ,安慰剂组血压、单肾 /体重值、2 4h尿蛋白排出量增加 ,肾脏有较明显的组织学改变 (如肾小球硬化 ;肾小管扩张、肥厚 ;蛋白管型 ;肾间质细胞浸润 ;小动脉壁增厚等 ) ,肾内转化生长因子 β1(TGF β1)和Smad7的蛋白表达明显上调。波生坦能较显著地缓解上述异常 (P <0 .0 5 )。 结论　波生坦对DHR肾脏有明显的保护作用 ,其机制可能与它能阻断内皮素系统以及下调TGF β1和Smad7有关。Objective To investigate the effects of endothelin receptor antagonist bosentan on progression of renal injury in DOCA-salt hypertensive rats(DHR).Methods 28 male Sprague-Dawley rats were unilaterally nephrectomized,given penicillin three days.Survived rats were randomly divided into 4 groups.Control group drinks tap water.Three other groups were administered DOCA subcutaneously and 1% saline;0.2% potassium chloride was added to their tap water for drinking.Simutaneously,they were given placebo,bosentan and amlodipine.Systolic blood pressure(SBP),24 hour urinary protein excretion rate,serum blood urea nitrogen(BUN) were measured.Renal histology change was assessed on PAS-staind sections.The protein expressions of renal transforming growth factor (TGF-β1) and Smad7 were determined by immunohistochemistry at 5th week.Results Enhanced urinary protein excretion,increased renal histology change,over-expressions of TGF-β1 and Smad7 were observed in untreated DHR compared with control group.All these abnormalities were ameliorated by bosentan. Conclusion Bosentan significantly attenuate renal damage in DHR probably by blocked endothelin system and decreasing the expression of TGF-β1 and Smad7.

关 键 词：波生坦 高血压 大鼠 肾脏保护 内皮素受体阻断剂 肾损害 

分 类 号：R544.1[医药卫生—心血管疾病] R692[医药卫生—内科学]