培哚普利对实验性糖尿病大鼠肾小管上皮细胞凋亡的影响  

Role of perindopril in the apoptosis in renal tubular in experimental diabetic rats

作　　者：邵牧民[1] 徐华[1] 孙惠力[2] 程小燕[2] 戈娜[2] 李顺民[2] 

机构地区：[1]广州中医药大学深圳附属医院病理科,广东深圳518033 [2]广州中医药大学深圳附属医院肾内科,广东深圳518033

出　　处：《安徽医药》2010年第10期1131-1133,共3页Anhui Medical and Pharmaceutical Journal

基　　金：广东省科技计划项目(No83109)

摘　　要：目的探讨培哚普利对实验性糖尿病大鼠肾小管上皮细胞凋亡的影响。方法链脲佐菌素（Streptozotocin,STZ）诱导的糖尿病大鼠模型,随机分为糖尿病组和培哚普利治疗组,另以正常大鼠作为对照组,共观察24周。于24周末检测各组大鼠血糖,血压,24 h尿白蛋白定量,肾重/体重。TUNEL检测小管细胞凋亡。免疫组织化学检测肾组织葡萄糖调节蛋白（glucose-reg-ulated protein-78,GRP78）蛋白的表达。结果糖尿病组和治疗组血糖明显高于正常组,但治疗组和糖尿病组差异无显著性。糖尿病模型组尿白蛋白水平均显著高于正常组,培哚普利治疗组尿白蛋白水平较模型组降低。糖尿病模型大鼠肾脏内TUNEL阳性细胞数、内质网应激相关蛋白GRP78的表达水平均较正常组明显升高。培哚普利能明显减少糖尿病大鼠肾脏内TUNEL阳性细胞数并降低内质网应激相关蛋白的表达。结论血管紧张素转换酶抑制剂可以减少实验性糖尿病大鼠肾小管上皮细胞凋亡,可能与其减少内质网应激的激活有关。Aim To investigate the role of perindopril in the apoptosis in renal tubular in experimental diabetic rats.Methods Diabe-tes was induced in male Sprague-Dawley rats by injection with streptozotocin at 60 mg.kg-1 i.p.Diabetic rats were then randomly as-signed into control（untreated） or treatment of an ACE inhibitor,perindopril,for 24 weeks.Tubule apoptosis was detected by TUNEL as-say.Endoplasmic reticulum stress associated proteins expression of glucose-regulated protein-78（GRP78） was assessed by immunohisto-chemistry.Results There were more TUNEL-positive nuclei in diabetic kidneys than in control kidneys.At 24 weeks,experimental dia-betes was associated with a considerable increase in protein expression of GRP78 in the tubulointestitium.ACE inhibitor not only attenua-ted the apoptosis but also reduced the overexpression of the endoplasmic reticulum stress associated protein in tubulointestitium of diabet-ic rats.Conclusion Increased tubular apoptosis in experimental diabetic rats is attenuated by blockade of the renin-angiotensin system with an ACE inhibitor,which might be in an association with reduced endoplasmic reticulum stress.

关 键 词：糖尿病肾病 凋亡 血管紧张素转换酶抑制剂 

分 类 号：R96[医药卫生—药理学]