缬沙坦对自发性高血压大鼠肾脏结构与功能的保护作用
作者：竺艳娟 傅辰生 蒋金根 廖履坦 丁小强
单位：200032 上海医科大学附属中山医院肾内科
关键词：大鼠，自发性高血压；血管紧张素Ⅱ受体拮抗剂；一氧化氮；转化生长因子β1；肾小动脉硬化
中华肾脏病杂志000510摘 要：目的探讨缬沙坦对自发性高血压大鼠(SHR)肾结构与功能的保护作用及其机制。方法将20只SHR随机分为3组，治疗组分别以苯那普利(10mg·kg-1·d-1)和缬沙坦(10mg·kg-1·d-1)灌胃12周，观察大鼠的血压、尿蛋白、血和尿一氧化氮(NO)水平及肾组织病理改变；并用逆转录-聚合酶链反应(RT-PCR)方法测定肾皮质转化生长因子β1(TGF-β1)mRNA表达。结果缬沙坦和苯那普利治疗组的尿蛋白显著减少(P<0.01)，且缬沙坦作用较苯那普利更显著(P<0.05)；两治疗组的血、尿NO水平升高(P<0.01)；TGF-β1mRNA表达水平下调(P<0.001)，缬沙坦组更明显(P<0.001)c病理上对照组大鼠肾小动脉壁显著增生肥厚，管腔狭窄甚至闭锁，个别小球硬化；而缬沙坦和苯那普利组的肾小动脉结构正常，未见小球硬化。结论缬沙坦能显著减少尿蛋白，逆转SHR肾小动脉硬化改变，保护肾功能，其机制可能有血管紧张素Ⅱ、NO和TGP-β1参与。
, http://www.100md.com
Nephroprotection of valsartan on function and morphology in spontaneously hypertensive rats
ZHU Yanjuan ,FU Chensheng ,JIANG Jingen,et al.
(Division of Nephrology,Zhongshan Hospital,Shanghai Medical University,Shanghai 200032,China)
Abstract：Objective To study the effect of vaIsartan on renal structure and function in spontaneously hypertensive rat(SHR) and explore its mechanism.Methods Twenty SHRs were gorged with benazepril (10 mg·kg-1·d-1),valsartan (10mg·kg-1·d-1) or water respectively for 12 weeks in the treating and control groups.The blood pressure,proteinuria and nitric oxide (NO) were assessed,and renal tissues were examined routinely by light and electron microscopy.The levels of TGF-β1 mRNA were detected by RT-PCR.Results The excretion of proteinuria significantly decreased in the treating groups compared to control group(P<0.01),and was further lower in valsartan group(P<0.05).The NO levels of serum and urine in the treating groups were significantly higher than that in the control(P<0.01).The levels of TGF-β1 mRNA were down-regulated in the treating groups(P<0.001),and further lower in valsartan group(P<0.001).Severe hypertrophy and sclerosis on the walls of arterioles,narrow,even occlusion in the lumina of these arterioles and hyalinization in some glomeruli were seen in control SHR.Benazepril and valsartan could attenuate the above injuries of small arteries.There was no hyalinization in glomernli and arterioles.Conclusions Valsartan reduces the extent of proteinuria and attenuates functional and structural injuries induced by hypertension.Angiotensin Ⅱ,NO and TGF-β1 may be involved in the mechanism concerned.
, 百拇医药
Keywords：Rat,spontaneously hypertensive;Angiotensin Ⅱ receptor antagonist;Nitric oxide;Transforming growth factor-β1;Renal arterial sclerosis
参考文献：
[1]Scott E,Campbell K,Laxmansa C.Angiotensin Ⅱ stimulated expression of transforming growth factor-β1 in cardiac fibroblasts and myofibroblasts.J Mol Cell Cardiol,1997,29:1947-1958.
[2]Nordlander M,Havu N.Effects of chronic felodipinc treatment on renal function and morphology in SHR.Kidney Int,1992,4-1 Supple 36:S100-S105.
, http://www.100md.com
[3]Maschio G,Albeti D,Janin G,et al.For the AIPRI Study Group.Effect of the angiotensin-converting enzyme inhibitor benazepril on the progression of chronic renal failure.N Engl J Med,1996,334:939-945.
[4]Remuzzi A,Fassi A,Sangalli F,et al.Prevention of renal injury in diabetic MWF rats by angiotensin Ⅱ antagonist.Exp Nephol,1998,6:28-38.
[5]Rosaura M,Cid JN,Garcia RM,et al.Losartan reduces phenylephrine constrictor response in aortic rings from spontaneously hypertensive rats:role of nitric oxide and angiotensin Ⅱ type 2 receptors.Hypertension,1996,28:967-972.
, 百拇医药
[6]Madrid MI,Garcia S M,Tornal J,et al.Interactions between nitric oxide and angiotensin Ⅱ on renal cortical and papillary blood flow.Hypertension,1997,30:1175-1182.
[7]Wu L L,Cox A,Roe C J,et al.Transforming growth factor β1 and renal injury following subtotal nephrectomy in the rat:role of the renin angioten system.Kidney Int,1997,51:1553-1567.
收稿日期：1999-11-10, http://www.100md.com
单位：200032 上海医科大学附属中山医院肾内科
关键词：大鼠，自发性高血压；血管紧张素Ⅱ受体拮抗剂；一氧化氮；转化生长因子β1；肾小动脉硬化
中华肾脏病杂志000510摘 要：目的探讨缬沙坦对自发性高血压大鼠(SHR)肾结构与功能的保护作用及其机制。方法将20只SHR随机分为3组，治疗组分别以苯那普利(10mg·kg-1·d-1)和缬沙坦(10mg·kg-1·d-1)灌胃12周，观察大鼠的血压、尿蛋白、血和尿一氧化氮(NO)水平及肾组织病理改变；并用逆转录-聚合酶链反应(RT-PCR)方法测定肾皮质转化生长因子β1(TGF-β1)mRNA表达。结果缬沙坦和苯那普利治疗组的尿蛋白显著减少(P<0.01)，且缬沙坦作用较苯那普利更显著(P<0.05)；两治疗组的血、尿NO水平升高(P<0.01)；TGF-β1mRNA表达水平下调(P<0.001)，缬沙坦组更明显(P<0.001)c病理上对照组大鼠肾小动脉壁显著增生肥厚，管腔狭窄甚至闭锁，个别小球硬化；而缬沙坦和苯那普利组的肾小动脉结构正常，未见小球硬化。结论缬沙坦能显著减少尿蛋白，逆转SHR肾小动脉硬化改变，保护肾功能，其机制可能有血管紧张素Ⅱ、NO和TGP-β1参与。
, http://www.100md.com
Nephroprotection of valsartan on function and morphology in spontaneously hypertensive rats
ZHU Yanjuan ,FU Chensheng ,JIANG Jingen,et al.
(Division of Nephrology,Zhongshan Hospital,Shanghai Medical University,Shanghai 200032,China)
Abstract：Objective To study the effect of vaIsartan on renal structure and function in spontaneously hypertensive rat(SHR) and explore its mechanism.Methods Twenty SHRs were gorged with benazepril (10 mg·kg-1·d-1),valsartan (10mg·kg-1·d-1) or water respectively for 12 weeks in the treating and control groups.The blood pressure,proteinuria and nitric oxide (NO) were assessed,and renal tissues were examined routinely by light and electron microscopy.The levels of TGF-β1 mRNA were detected by RT-PCR.Results The excretion of proteinuria significantly decreased in the treating groups compared to control group(P<0.01),and was further lower in valsartan group(P<0.05).The NO levels of serum and urine in the treating groups were significantly higher than that in the control(P<0.01).The levels of TGF-β1 mRNA were down-regulated in the treating groups(P<0.001),and further lower in valsartan group(P<0.001).Severe hypertrophy and sclerosis on the walls of arterioles,narrow,even occlusion in the lumina of these arterioles and hyalinization in some glomeruli were seen in control SHR.Benazepril and valsartan could attenuate the above injuries of small arteries.There was no hyalinization in glomernli and arterioles.Conclusions Valsartan reduces the extent of proteinuria and attenuates functional and structural injuries induced by hypertension.Angiotensin Ⅱ,NO and TGF-β1 may be involved in the mechanism concerned.
, 百拇医药
Keywords：Rat,spontaneously hypertensive;Angiotensin Ⅱ receptor antagonist;Nitric oxide;Transforming growth factor-β1;Renal arterial sclerosis
参考文献：
[1]Scott E,Campbell K,Laxmansa C.Angiotensin Ⅱ stimulated expression of transforming growth factor-β1 in cardiac fibroblasts and myofibroblasts.J Mol Cell Cardiol,1997,29:1947-1958.
[2]Nordlander M,Havu N.Effects of chronic felodipinc treatment on renal function and morphology in SHR.Kidney Int,1992,4-1 Supple 36:S100-S105.
, http://www.100md.com
[3]Maschio G,Albeti D,Janin G,et al.For the AIPRI Study Group.Effect of the angiotensin-converting enzyme inhibitor benazepril on the progression of chronic renal failure.N Engl J Med,1996,334:939-945.
[4]Remuzzi A,Fassi A,Sangalli F,et al.Prevention of renal injury in diabetic MWF rats by angiotensin Ⅱ antagonist.Exp Nephol,1998,6:28-38.
[5]Rosaura M,Cid JN,Garcia RM,et al.Losartan reduces phenylephrine constrictor response in aortic rings from spontaneously hypertensive rats:role of nitric oxide and angiotensin Ⅱ type 2 receptors.Hypertension,1996,28:967-972.
, 百拇医药
[6]Madrid MI,Garcia S M,Tornal J,et al.Interactions between nitric oxide and angiotensin Ⅱ on renal cortical and papillary blood flow.Hypertension,1997,30:1175-1182.
[7]Wu L L,Cox A,Roe C J,et al.Transforming growth factor β1 and renal injury following subtotal nephrectomy in the rat:role of the renin angioten system.Kidney Int,1997,51:1553-1567.
收稿日期：1999-11-10, http://www.100md.com