L-精氨酸和氨基胍对糖尿病大鼠一氧化氮、一氧化氮合酶及肾功能的影响
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中国留学基金资助项目(留进出[1999]3053);;山东省优秀中青年科学家科研奖励基金(2004BS02016)


Antithetic Investigation of L-Anginine and Aminoguanidine on Nitric Oxide,Nitric Oxide Synthase and Renal Function of Diabetic Rats
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    摘要:

    目的探讨L-精氨酸和氨基胍对早期糖尿病大鼠一氧化氮、一氧化氮合酶活性及肾功能的影响。方法Wistar大鼠60只,检测其24 h尿蛋白排泄量、血清一氧化氮水平、总一氧化氮合酶和诱导型一氧化氮合酶及结构型一氧化氮合酶活性等5项指标。然后用链脲佐菌素60 mg/kg制备糖尿病大鼠模型,将糖尿病鼠随机分为糖尿病对照组、L-精氨酸组和氨基胍组。于8周末时再检测大鼠上述5项指标并进行统计分析。结果与造模前比较,糖尿病对照组在8周末时24 h尿蛋白排泄量(43.92±7.38 mg)、一氧化氮水平(42.2±6.92μmol/L)和诱导型一氧化氮合酶活性(19.75±3.85 kU/L)升高(p<0.01,p<0.05);L-精氨酸组24 h尿蛋白排泄量(100.47±43.42 mg)和一氧化氮水平(67.34±18.87μmol/L)显著升高(p<0.01);氨基胍组24 h尿蛋白排泄量(22.33±3.47 mg)增加(p<0.01),总一氧化氮合酶(23.34±3.10 kU/L)、诱导型一氧化氮合酶(14.84±1.98 kU/L)和结构型一氧化氮合酶(8.50±2.25 kU/L)降低(p<0.01,p<0.05)。与糖尿病对照组比较,8周末时L-精氨酸组24 h尿蛋白排泄量和一氧化氮均升高(p<0.05),总一氧化氮合酶、诱导型一氧化氮合酶和结构型一氧化氮合酶活性差异无显著性;氨基胍组与L-精氨酸组比较,上述5项指标均下降(p<0.05)。结论在糖尿病肾病早期应用L-精氨酸可增加血一氧化氮的合成,使24 h尿蛋白排泄量增加,损害肾功能;而早期应用氨基胍可降低血一氧化氮、一氧化氮合酶及24 h尿蛋白排泄量,保护肾功能。

    Abstract:

    Aim To investigate the effect of L-Aanginine and aminoguanidine on serum nitric oxide,nitric oxide synthase activity and renal function of diabetic rats. Methods Sixty healthy Wistar rats were involved in the study.The 24 hr urinary protein excretion(UPE),serum levels of nitric oxide(NO), total nitric oxide synthase(NOS) activity,inducible nitric oxide synthase activity and constructive nitric oxide synthase activity were detected to the rats.Streptozotocin(60 mg/kg) was administrated in the rats.The Streptozotocin(STZ) diabetic rats were randomly divided into diabetes control group,L-aanginine group and aminoguanidine group.At the end of 8 weeks after STZ administration,the above five indexes of the rats were detected and statistical analysis was carried out. Results Compared with normal rats: 24hUPE(43.92±7.38 mg),iNOS(19.75±3.85 kU/L) and NO(42.2±6.92 μmol/L) of the rats in diabetes(DM) control group increased significantly(p<0.01,p<0.05).In the rats of L-aanginine group,both 24hUPE(100.47±43.42 mg) and NO(67.34±18.87 μmol/L) increased significantly(p<0.01).In the rats of Aminoguanidine group,24hUPE(22.33±3.47 mg) increased while both tNOS(23.34±3.10 kU/L),iNOS(14.84±1.98 kU/L) and cNOS(8.50±2.25 kU/L) decreased(p<0.01,p<0.05).Compared with the diabetes control group,both 24hUPE and NO increased(p<0.05) in L-aang group at the end of 8 weeks.There was no obvious differences in tNOS,iNOS and cNOS levels in L-aanginine group,and the five indexes were significantly decreased in Aminoguanidine group(p<0.05).Compared with L-aang group,the five indexes were obviously decreased in Aminoguanidine group(p<0.05). Conclusion In early stage of diabetic nephropathy,administration of L-aanginine is harmful to the renal function while aminoguanidine is beneficial to the kidney via increasing or decreasing NO and NOS.

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潘振宇,赵家军,廖琳. L-精氨酸和氨基胍对糖尿病大鼠一氧化氮、一氧化氮合酶及肾功能的影响[J].中国动脉硬化杂志,2006,14(10):845~848.

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  • 收稿日期:2006-05-09
  • 最后修改日期:2006-09-20
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