吡格列酮对早期糖尿病肾病大鼠血清一氧化氮和一氧化氮合酶的影响  

Pioglitazone reduces serum nitric oxide and nitricoxide synthase in rats with early diabetic nephropathy

作　　者：杨前勇[1] 聂忠[1] 宋宁燕[1] 

机构地区：[1]解放军第九四医院内分泌科

出　　处：《医学研究生学报》2011年第9期904-907,共4页Journal of Medical Postgraduates

摘　　要：目的糖尿病肾病(diabetic nephropathy,DN)是糖尿病的慢性并发症和主要死因,其发病机制复杂,缺乏明确有效治疗措施。文中探讨血清一氧化氮(nitric oxide,NO)、一氮化氮合酶(nitric oxide synthase,NOS)与DN的关系及吡格列酮(P ioglitazone)对其影响。方法采用链脲佐菌素诱导糖尿病模型,随机分为正常对照组、正常对照治疗组、糖尿病组、糖尿病治疗组,2治疗组给予吡格列酮10mg/(kg.d)灌胃,每组10只。第10周末测定血糖、肾重/体重、24 h尿蛋白定量;检测各组血清NO含量及总一氧化氮合酶(total nitric oxide synthases,T-NOS)、诱导型一氧化氮合酶(inducible nitric oxide synthases,iNOS)和结构型一氧化氮合酶(constructure nitric oxide synthases,cNOS)活性。结果糖尿病治疗组与糖尿病组比较,血糖无显著差异(P>0.05),但肾重/体重和24 h尿蛋白定量明显降低(P<0.01)。糖尿病组NO水平和T-NOS、iNOS活性较正常对照组明显增加(P<0.05或0.01),糖尿病治疗组NO水平和T-NOS、iNOS活性较糖尿病组明显下降(P<0.05或0.01)。cNOS活性各组间比较无显著差异(P>0.05)。结论早期DN大鼠血清NO含量和iNOS活性明显升高。吡格列酮非降糖的肾保护作用可能与其抑制iNOS活性和减少NO生成有关。Objective Diabetic nephropathy（DN） is one of the common complications and a major cause of mortality in diabetes mellitus（DM）.Its pathogenesis is so complicated that there are no definitely effective approaches to its management.This research was to investigate the changes of serum nitric oxide（NO） and nitricoxide synthase（NOS） in rats with early DN and their response to pioglitazone.Methods Forty male Wistar rats were randomly divided into four groups of equal number： normal control（NC）,NC with pioglitazone（NCT）,DM,and DM with pioglitazone（DMT）.DM models were induced by streptozotocin.The rats in the NCT and DMT groups were treated intragastrically with pioglitazone at 10 mg/（kg·d）.The serum NO concentration and activities of T-NOS,iNOS,cNOS were measured at the end of the tenth week.Results There were no significant differences in the NO level and T-NOS and iNOS activities between the NCT and NC groups（P0.05）.The increased NO level and T-NOS and iNOS activities in diabetic rats were significantly attenuated by pioglitazone treatment（P0.05 or 0.01）.No significant differences were found in cNOS activity among the four groups（P0.05）.Conclusion The serum NO level and iNOS activity are markedly elevated in early DN rats.Pioglitazone protects the kidney by lowering the NO level and iNOS activity.

关 键 词：噻唑烷二酮 吡格列酮 糖尿病肾病 一氧化氮 一氧化氮合酶 

分 类 号：R582.2[医药卫生—内分泌]