期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

吡咯烷二硫代氨基甲酸酯对2型糖尿病大鼠肾脏的保护作用 被引量：8

Protective effect of pyrrolidine dithiocarbamate on kidneys in type 2 diabetic rats
下载PDF
导出
摘要 目的:探讨吡咯烷二硫代氨基甲酸酯(PDTC)对2型糖尿病大鼠肾脏的保护作用及其机制。方法:雄性Wistar大鼠,随机分为2组:正常对照(NC)组和高脂饮食(HFD)组。喂养8周后高脂饮食组大鼠腹腔注射小剂量链脲佐菌素(STZ,27 mg/kg),以随机血糖≥16.7 mmol/L为2型糖尿病大鼠造模成功。将成模大鼠随机分为2组:糖尿病模型(DM)组和PDTC(50 mg.kg-1.d-1,ip)治疗组。治疗1周后断头处死大鼠,留取各组血浆、尿液及肾脏标本。测定各组血糖、尿微量白蛋白/肌酐比值、肾皮质组织中丙二醛(MDA)的含量、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的活性;经HE及Masson染色观察大鼠肾小球形态学变化;透射电镜观察肾脏微血管超微结构改变;免疫组化观察肾脏组织中诱生型一氧化氮合酶(iNOS)和硝基酪氨酸(NT)的表达。结果:PDTC治疗组血糖和尿微量白蛋白/肌酐比值较DM组明显降低(P<0.01)。DM组肾皮质组织中MDA含量明显高于NC组,GSH-Px和SOD的活性明显低于NC组(P<0.05)。HE及Masson染色显示,DM组肾小球体积增大,肾小管扩张,系膜区扩张,Masson染色阳性物质增多,提示肾小球毛细血管基底膜增厚;PDTC治疗组病理改变较DM组明显改善。电镜超微结构显示,DM组基底膜高度增厚,厚度不均,有断裂层,足突融合;PDTC治疗组基底膜轻度增厚,足突轻度融合。免疫组化显示,DM组iNOS和NT表达量较NC组明显增多(P<0.05);PDTC治疗组iNOS和NT表达量较DM组明显减少(P<0.05)。结论:PDTC不仅具有降低血糖作用,而且可通过减少iN-OS和NT表达改善糖尿病肾脏损害。 AIM： To investigate the protective effect of pyrrolidine dithiocarbamate （PDTC） on the kidneys in type 2 diabetic rats. METHODS： High-fat diet and a small dose （27 mg/kg） of streptozotocin -induced diabetic rats were treated with or without PDTC （50 mg·kg-1·d-1, ip） for 1 week, and age -matched nondiabetic animals were also used for comparison. The concentration of malondialdehyde （MDA）and the activity of superoxide dismutase （SOD） and glutathione peroxidasc （ GSH - Px） were determined by commercial kit. The ratio of urine microalbumin/creatinine was measured by an automatic biochemical analyzer. The morphological changes of renal glomerulus were observed by HE/Mas- son staining and transmission electron microscopy. The expression of inducible nitric oxide synthase （iNOS） and nitrotyrosine （NT） in the renal tissues was examined by the method of immunohistochemistry. RESULTS： PDTC -treated rats had lower blood glucose level and urine microalbumin/creatinine ratio than those in untreated diabetic rats. The levels of tissue MDA in diabetic rats were significantly higher, and the activity of SOD and GSH - Px was lower than those in normal control rats （P 〈 0. 05）. The renal damage in diabetic rats was significantly improved after PDTC treatment. PDTC administration markedly attenuated the expression of iNOS and the production of NT in renal glomerulus and tubule in diabetic rats. CONCLUSION： PDTC not only reduces blood glucose level, but also protects the diabetic rats from diabetic nephmpathy by diminishing the expression of iNOS and the production of NT.
作者 张新杰 刘建坤 高冬梅 张怡梅 朱铁年 赵瑞景
机构地区 白求恩国际和平医院肿瘤科 邯郸市中心医院内分泌科 河北医科大学免疫学教研室
出处 《中国病理生理杂志》 CAS CSCD 北大核心 2012年第10期1807-1811,共5页 Chinese Journal of Pathophysiology
基金 河北省自然科学基金资助项目(No.C2009001232) 河北省科技支撑计划项目(No.10276105D-66) 河北省卫生厅资助项目(No.20090168) 国家人事部留学人员科技活动项目择优资助项目(2008年度) 河北省教育厅资助项目(No.2008135)
关键词 糖尿病肾病 吡咯烷二硫代氨基甲酸酯 氧化性应激 一氧化氮合酶 硝基酪氨酸 Diabetic nephropathies Pyrrolidine dithiocarbamate Oxidative stress Nitric oxide synthase Nitrotyrosine
分类号 R587.1 [医药卫生—内分泌]
  • 相关文献

参考文献12

  • 1Jenkins A J, Best JD, Klein RL, et al. Lipoproteins, gly- coxidation and diabetic angiopathy [ J ]. Diabetes Metab Res Rev, 2004, 20 (5) : 349 - 368.
  • 2Reed MJ, Meszaros K, Entes LJ, et al. A new rat model of type 2 diabetes: the fat - fed, streptozotocin - treated rat[J]. Metabolism, 2000, 49(11) : 1390 - 1394.
  • 3Dronavalli S, Duka I, Bakris GL. The pathogenesis of di- abetic nephropathy [ J ]. J Nat Clin Pract Endocrinol Metab, 2008, 4(8):444-452.
  • 4Ha H, Yu MR, Choi YJ, et al. Role of high glucose - in- duced nuclear factor - KB activation in monocyte chemoat- tractant protein - 1 expression by mesangial cells [ J ]. J Am Soc Nephrol, 2002, 13(4) :894 -902.
  • 5Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Compli- cations and Research Group. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus [J]. JAMA, 2002, 287(19):2563-2569.
  • 6Kaneto H, Matsuoka TA, Katakami N, et al. Oxidative stress and the JNK pathway are involved in the develop- ment of type 1 and type 2 diabetes [ J ]. Curr Mol Med, 2007, 7(7) :674 -686.
  • 7Obrosova IG. Increased sorbitol pathway activity generates oxidative stress in tissue sites for diabetic complications [ J ]. Antioxid Redox Signal, 2005, 7 ( 11 - 12 ) : 1543 - 1552.
  • 8Kolodziejska KE, Bums AR, Moore RH, et al. Regula- tion of inducible nitric oxide synthase by aggresome forma- tion[J]. Proc Nail Acad Sci U S A, 2005, 102(13): 4854 - 4859.
  • 9Ali TK, Matragoon S, Pillai BA, et al. Peroxynitrite me- diates retinal neurodegeneration by inhibiting nerve growth factor survival signaling in experimental and human diabe- tes [ J ]. Diabetes, 2008, 57 (4) : 889 - 898.
  • 10Peluffo G, Radi R. Biochemistry of protein tyrosine nitra- tion in cardiovascular pathology [ J 1. Cardiovasc Res, 2007, 75 (2) :291 - 302.

二级参考文献14

  • 1Moh A,Zhang WJ,Yu S,et al.STAT3 sensitizes insulin signaling by negatively regulating glycogen synthase kinase-3[J].Diabetes,2008,57(5):1227-1235.
  • 2Grimes CA,Jope RS.The multifaceted roles of glycogen synthase kinase 3 in cellular signaling[J].Prog Neurobiol,2001,65(4):391-426.
  • 3Tomiyasu M,Obataa T,Nishia Y,et al.Monitoring of liver glycogen synthesis in diabetic patients using carbon-13 MR spectroscopy[J].Eur J Radiol,2010,73 (2):300-304.
  • 4Liberman Z,Eldar-Finkelman H.Serine 332 phosphorylation of insulin receptor substrate-1 by glycogen synthase kinase-3 attenuates insulin signaling[J].J Biol Chem,2005,280(6):4422-4428.
  • 5Gupta S,Young D,Sen S,et al.Inhibition of NF-κB induces regression of cardiac hypertrophy,independent of blood pressure contorl,in spontaneously hypertensive rats[J].Am J Physiol Heart Circ Physiol,2005,289(1):H20-H29.
  • 6Malm TM,Iivonen H,Goldsteins G,et al.Pyrrolidine dithiocarbamate activates Akt and improves spatial learning in APP/PS1 mice without affecting β-amyloid burden[J].J Neurosci,2007,27(14):3712-3721.
  • 7Amin MA,Ruth JH,Haas CS,et al.H-2g,a glucose analog of blood group H antigen,mediates mononuclear cell recruitment via Src and phosphatidylinositol 3-kinase pathways[J].Arthritis Rheum,2008,58(3):689-695.
  • 8Stosic-Grujicic SD,Miljkovic DM,Cvetkovi ID,et al.Immunosuppressive and anti-inflammatory action of antioxidants in rat autoimmune diabetes[J].J Autoimmun,2004,22(4):267-276.
  • 9Lee FT,Cao Z,Long DM,et al.Interactions between angiotensin II and NF-κB-dependent pathways in modulating macrophage infiltration in experimental diabetic nephropathy[J].J Am Soc Nephrol,2004,15(8):2139-2151.
  • 10Patel S,Doble B,Woodgett JR.Glycogen synthase kinase-3 in insulin and Wnt signalling:a double-edged sword?[J].Biochem Soc Trans,2004,32(Pt5):803-808.

共引文献3

同被引文献72

引证文献8

二级引证文献74

中国病理生理杂志
2012年 第10期

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部