邹敏书 刘雪梅 余健 聂国明 (广州军区武汉总医院儿科 武汉 430070)
摘 要 目的：观察贝那普利及维生素E对糖尿病肾病（DN）大鼠肾脏一氧化氮合成酶（NOS）活性、一氧化氮(NO)，超氧化物歧化酶（SOD）、丙二醛（MDA）含量及血清总抗氧化能力的影响，探讨两者在DN中的可能作用机制。方法：注射链佐脲菌素制作DN模型，分为4组，A组：正常对照组；B组：糖尿病肾病模型组；C组：贝那普利治疗组；D组：贝那普利+维生素E治疗组。于第12周检测24 h尿蛋白定量（TP）、血清胱蛋白酶抑制剂C（Cys C）、糖化血红蛋白(HbAlc)，血清总抗氧化能力，肾组织NOS、NO、SOD、MDA含量。结果：与A组相比，B组TP、CysC、HbAlc、肾组织血糖、MDA明显升高（P＜0.01)，而血清总抗氧化能力，肾组织NO、NOS、SOD明显降低（P＜0.01)。与B组相比，C组TP、CysC、HbAlc、肾组织血糖显著降低（P＜0.01)，MDA亦下降（P＜0.05)，而总抗氧化能力增强（P＜0.05)，SOD升高（P＜0.01)。与C组相比，D组TP、肾组织血糖下降更加显著（P＜0.01)，MDA下降（P＜0.05)，而NO、NOS、SOD明显升高（P＜0.05或P＜0.01)，总抗氧化能力增强（P＜0.05)。结论：贝那普利能降低TP、HbAlc、肾组织血糖、MDA，增加NO、NOS、SOD，维生素E可增加血清总抗氧化能力，清除自由基而有肾保护作用。两者对治疗DN氧化应激有协同作用。
关键词 贝那普利；维生素E；糖尿病肾病
中图分类号：R965.1
文献标识码：A
文章编号：1008-049X(2007)06-0525-03
Effects of Benazepril and Vitamin E on Oxidative Stress in Diabetic Nephropathy Rats
Zou Minshu,Liu Xuemei,Yu Jian, Nie Guoming(Department of pediatrics,Wuhan General Hospital, Guangzhou military command, Wuhan 430070, China)
ABSTRACT Objective: To observe the effects of Benazepril and vitamin E on the activity of renal nitric oxide synthetase(NOS), levels of renal nitric oxide(NO), superoxide dismutase(SOD), malonaldehyde(MDA) and the total antioxidant capability of serum(TAC) with diabetic nephropathy(DN) rats. To investigate the possible mechanism of the two drugs involved in DN. Method: Diabetic rats were induced by streptozotocin(STZ). There were divided into four groups: normal control group(group A), diabetic model group(group B), benazepril treated group(group C), benazepril and vitamin E treated group(group D). 24h total proteinuria(TP), Serum Cystatin C(Cys C), glucosylated hemoglobin(HbAlc), TAC, the activity of renal NOS, renal content of NO,SOD,MDA were assayed respectively. Result: Compared with group A, TP, CysC, HbAlc, the glouse of kidney tissue(RG), MDA in group B were significantly higher（P＜0.01).TAC the level of NO, NOS, SOD in renal tissue were lower（P＜0.01).Compared with group B, TP, CysC, HbAlc, RG in group C were significantly decreased（P＜0.01),MDA was decreased aslo（P＜0.05). TAC was enhanced（P＜0.05),SOD were increased also（P＜0.01).Compared with group C,TP,RG,MDA were significantly decreased in group D（P＜0.01),and MDA also decreased（P＜0.05).However,NO,NOS,SOD significantly increased（P＜0.05 or P＜0.01),TAC was enhanced（P＜0.05）. Conclusion: Benazepril can decrease TP, HbAlc and RG, increase the level of NO,NOS,SOD in renal tissue, Vitamin E may be enhance TAC, scavenge free radical to protect kidney. The two drugs had a synergistic effect to treat oxidative stress in DN rats.
KEY WORDS Benazepril;Vitamin E;Diabetic nephropathy
参 考 文 献
1 Evans JL,Goldfine ID,Maddux BA,et al.Oxidative stress and stressactived signaling pathways:a unifying hypothesis of type 2 diabetes［J］.Endocrine Reviews,2002,23(5):599-622.
2 Zachary T, Bloomgarden MD.Diabetic nephropathy［J］. Diabetes Care,2005,28:745-751
3 Vincent AM,Russell JW,Feldman PE.et al.Oxidative stress in the pathogenesis of diabetic neuropathy［J］.Endocrine Reviews, 2004,25 (4): 612-628
4 Trachtman H,Futterweit S,Garg P,et al.Nitric oxide stimulates the activety of a 72KDa neutral matrix metalloproteinase in cultured rat mesangial cells［J］.Biochem Biophys Res Commun,1996,218:704-710
5 余健,邹敏书,聂国明,等.纳洛酮、苯巴比妥对重度窒息新生儿血浆内皮素和丙二醛的影响［J］.中国药师,2006,9(8):698-700
6 Huang HY, Appel LJ.Supplementation of diets with tocopherol reduces serum concentrations of and tocopherol in humans［J］.J Nutr,2003:133:3137-3140
7 林善锬.糖尿病肾病研究中的几个值得重视的问题［J］.中华肾脏病杂志,2004,20(3):151-153
8 Sharma R,Khanna A,Sharma A,et al.Transforming growth factor-β1 increases albumin permeability of isolated rat glomeruli via hydroxyl radicals［J］.Kidney Int,2000,58:131-136
9 Harrisonbernard LM,Imig JD,et al.Renal AT1R receptor protein expression during the early stage of edabetes millitus［J］.Int J Exp Diabetes Res,2002,3:97-108
10 顾勇,赖凌云.肾素血管紧张素系统在糖尿病肾病研究中的新进展［J］.中华肾脏病杂志,2004,20(3):221-223
11 涂晓文,王艳侠,张爱平,等.维生素E对大鼠糖尿病肾病的防治作用及其机制［J］.中华糖尿病杂志,2005,67-68 资料来自:中国药师-专业站 |