氯沙坦对糖尿病大鼠肾脏保护作用的探讨
作者：卢筱华 冯烈 许敏华
单位：510630 广州，暨南大学医学院第一附属医院内分泌科
关键词：糖尿病肾病；一氧化氮；内皮素；转化生长因子-β；氯沙坦
中华肾脏病杂志000311摘 要：目的探讨血管紧张素Ⅱ受体拮抗剂氯沙坦对糖尿病大鼠肾小球病变的保护作用及其机制。方法观察氯沙坦对糖尿病鼠肾血流量、肾脏体积及尿蛋白排泄的影响，以及对血、肾组织局部一氧化氮(NO)，内皮素(ET)、转化生长因子-β(TGP-β1)含量的影响。结果氯沙坦可降低尿白蛋白、β2，微球蛋白(β2-m)排泄率，肌酐清除率(Ccr)及阻遏早期肾小球肥大，且不同程度降低肾组织局部NO、ET含量，大剂量氯沙坦还能降低尿液中TGP-β1含量。结论氯沙坦对糖尿病肾脏有保护作用，此作用可能与氯沙坦降低肾组织局部NO、ET及TCF-β1水平有关。
Protective effects of Iosartan on diabetic glomerulopathy in STZ-induced diabetic rats
, 百拇医药
LU Xiaohua,FENG Lie,XU Minhua
(the First Affiliated Hospital of Medical College , Jinan University , Guangzhou 510630, China)
Abstract：Objective To evaluate the protective effects of specific antagonists of angiotensin Ⅱ receptor losartan on the kidneys of diabetic rats and study their mechanisms. Methods Changes of urinary albumin, β2-m excretion, creatinine clearance(Ccr), NO, ET level of plasma,urine and renal tissue, serum and urinary TGF-β1 concentration and mean glomerular volume were measured. Results Losartan could correct elevated urinary albumin, β2-m excretion, Ccr and mean glomerular volume. Urinary and renal tissue NO, ET concentration decreased after diabetic rats received Iosartan. Large doses of losartan also reduced urinary TGF-β1 level. Conclusion Losartan can protect the kidney of diabetic rats and the decrease of NO, ET, TGF-β1 concentration in renal tissue may be a mechanism for this action.
, 百拇医药
Keywords：Diabetic glomerulopathy; Nitric oxide; Endothelin; Transforming growth factor-β; Losartan
参考文献：
[1]Remuzzi A, Perico N, Amuchastegui CS, et al. Short and long-term effect of angiotensin Ⅱ receptor blockade in rats with experimental diabetes. J Am Soc Nephrol, 1993,4: 40-45.
[2]Kohzuki M, Yasujima M, Kanazawa M, et al. Antihypertensive and renal protective effects of Losartan in streptozotocin diabetic rats. J Hypertens, 1995, 13: 97-101.
, 百拇医药
[3]Yotsumoto T, Naitoh T, Shikada K, et al. Effects of specific antagonists of angiotensin Ⅱ receptors and captopril on diabetic nephropathy in mice. Jpn J Pharmacol, 1997, 75: 59-62.
[4]于德民，吴锐，尹潍，等.实验性链脲佐菌素糖尿病动物模型的研究.中国糖尿病杂志，1995，3：105-109.
[5]Tolins JP, Shultz PJ, Raij L, et al. Abnormal renal hemodynamic response to reduced renal perfusion pressure in diabetic rats: role of NO. Am J Physiol, 1993, 265: F886-F889.
, 百拇医药
[6]Trachtman H, Futterweit S, Sirghal P. Nitric oxide modulates the synthesis of extracellular matrix proteins in cultured rat mesangial cell. Biochem Biophys Res Commun, 1995, 207: 120-124.
[7]Leppaluoto J, Ruskoaho H. Endothelin peptides: biological activities cellular singalling and clinical significance. Ann Med, 1992, 24: 153-158.
[8]Simonson MS, Dunn MJ. Endothelin peptides: a possible role in glomerular inflammation. Lab Invest, 1991,64: 1-5.
, 百拇医药
[9]Sharma K, Ziyadeh FN. Perspectives in diabetes: hyperglycemia and diabetic kidney disease. The case for transforming growth factor as a key mediator. Diabetes, 1995, 44: 1139-1145.
[10]Rappaport RM, F Murad. Agonist induced endothelin-dependent relaxation in rat thoracic aorta may be mediated through cGMP. Cire Res, 1983, 52: 352-357.
[11]胡伟新，龚德华.血管紧张素Ⅱ在糖尿病肾病发病中的作用.肾脏病与透析肾移植杂志，1998，7：161-165.
收稿日期：1999-08-28, 百拇医药
单位：510630 广州，暨南大学医学院第一附属医院内分泌科
关键词：糖尿病肾病；一氧化氮；内皮素；转化生长因子-β；氯沙坦
中华肾脏病杂志000311摘 要：目的探讨血管紧张素Ⅱ受体拮抗剂氯沙坦对糖尿病大鼠肾小球病变的保护作用及其机制。方法观察氯沙坦对糖尿病鼠肾血流量、肾脏体积及尿蛋白排泄的影响，以及对血、肾组织局部一氧化氮(NO)，内皮素(ET)、转化生长因子-β(TGP-β1)含量的影响。结果氯沙坦可降低尿白蛋白、β2，微球蛋白(β2-m)排泄率，肌酐清除率(Ccr)及阻遏早期肾小球肥大，且不同程度降低肾组织局部NO、ET含量，大剂量氯沙坦还能降低尿液中TGP-β1含量。结论氯沙坦对糖尿病肾脏有保护作用，此作用可能与氯沙坦降低肾组织局部NO、ET及TCF-β1水平有关。
Protective effects of Iosartan on diabetic glomerulopathy in STZ-induced diabetic rats
, 百拇医药
LU Xiaohua,FENG Lie,XU Minhua
(the First Affiliated Hospital of Medical College , Jinan University , Guangzhou 510630, China)
Abstract：Objective To evaluate the protective effects of specific antagonists of angiotensin Ⅱ receptor losartan on the kidneys of diabetic rats and study their mechanisms. Methods Changes of urinary albumin, β2-m excretion, creatinine clearance(Ccr), NO, ET level of plasma,urine and renal tissue, serum and urinary TGF-β1 concentration and mean glomerular volume were measured. Results Losartan could correct elevated urinary albumin, β2-m excretion, Ccr and mean glomerular volume. Urinary and renal tissue NO, ET concentration decreased after diabetic rats received Iosartan. Large doses of losartan also reduced urinary TGF-β1 level. Conclusion Losartan can protect the kidney of diabetic rats and the decrease of NO, ET, TGF-β1 concentration in renal tissue may be a mechanism for this action.
, 百拇医药
Keywords：Diabetic glomerulopathy; Nitric oxide; Endothelin; Transforming growth factor-β; Losartan
参考文献：
[1]Remuzzi A, Perico N, Amuchastegui CS, et al. Short and long-term effect of angiotensin Ⅱ receptor blockade in rats with experimental diabetes. J Am Soc Nephrol, 1993,4: 40-45.
[2]Kohzuki M, Yasujima M, Kanazawa M, et al. Antihypertensive and renal protective effects of Losartan in streptozotocin diabetic rats. J Hypertens, 1995, 13: 97-101.
, 百拇医药
[3]Yotsumoto T, Naitoh T, Shikada K, et al. Effects of specific antagonists of angiotensin Ⅱ receptors and captopril on diabetic nephropathy in mice. Jpn J Pharmacol, 1997, 75: 59-62.
[4]于德民，吴锐，尹潍，等.实验性链脲佐菌素糖尿病动物模型的研究.中国糖尿病杂志，1995，3：105-109.
[5]Tolins JP, Shultz PJ, Raij L, et al. Abnormal renal hemodynamic response to reduced renal perfusion pressure in diabetic rats: role of NO. Am J Physiol, 1993, 265: F886-F889.
, 百拇医药
[6]Trachtman H, Futterweit S, Sirghal P. Nitric oxide modulates the synthesis of extracellular matrix proteins in cultured rat mesangial cell. Biochem Biophys Res Commun, 1995, 207: 120-124.
[7]Leppaluoto J, Ruskoaho H. Endothelin peptides: biological activities cellular singalling and clinical significance. Ann Med, 1992, 24: 153-158.
[8]Simonson MS, Dunn MJ. Endothelin peptides: a possible role in glomerular inflammation. Lab Invest, 1991,64: 1-5.
, 百拇医药
[9]Sharma K, Ziyadeh FN. Perspectives in diabetes: hyperglycemia and diabetic kidney disease. The case for transforming growth factor as a key mediator. Diabetes, 1995, 44: 1139-1145.
[10]Rappaport RM, F Murad. Agonist induced endothelin-dependent relaxation in rat thoracic aorta may be mediated through cGMP. Cire Res, 1983, 52: 352-357.
[11]胡伟新，龚德华.血管紧张素Ⅱ在糖尿病肾病发病中的作用.肾脏病与透析肾移植杂志，1998，7：161-165.
收稿日期：1999-08-28, 百拇医药