【摘要】 目的探讨多聚(ADP-核糖)聚合酶(PARP)抑制剂PJ34对糖尿病大鼠肾脏保护作用及其可能机制。方法将SD大鼠分为正常对照组、模型对照组、模型治疗组,模型治疗组给予PJ34 10mg/kg,正常对照组及模型对照组给予同等剂量的纯化水。测定尿白蛋白排泄量(UAE)、内生肌酐清除率(Ccr)、血浆及肾组织一氧化氮(NO)、一氧化氮合酶(NOS)、内皮素(ET)、转化生长因子β1(TGF-β1)和肾小球蛋白激酶C(PKC)水平,并行肾组织形态学观察。结果4周时,模型对照组Ccr、UAE、NO、NOS及肾小球细胞膜PKC明显高于正常对照组,ET低于正常对照组;8周时,糖尿病大鼠肾小球细胞膜PKC明显高于正常对照组,NO和NOS均低于正常对照组,ET高于正常对照组。8周时模型治疗组大鼠的Ccr、尿白蛋白量和肾小球细胞膜PKC,以及4周时NO、NOS明显低于模型对照组。模型治疗组的肾功能及肾病变明显改善,肾组织中ET水平、TGF-β1表达减少。结论PJ34对糖尿病大鼠的肾脏有保护作用,可能与抑制PKC、肾脏NO合成及降低肾组织ET和TGF-β1水平有关。更多还原

【Abstract】 Objective To study the renal protection and action mechanism of poly (ADP-ribose) polymerase(PARP) inhibitor PJ34 on streptozotocin induced diabetic rats.Methods SD rats were randomized into control group,model group and experiment group.The experiment group received intraperitoneal injection of PJ34(10mg/kg),while other two groups accepted purified water.Urinary albumin excretion(UAE),creatinine clearance rate(Ccr),plasma and renal levels of nitric oxide(NO) and nitric oxide synthase(NOS),renal levels of endothelin(ET) and the transforming growth factor β1(TGF-β1),and glomerular expression of protein kinase C(PKC),as well as morphology of renal tissue were determined.Results Ccr,UAE,and expression of NO,NOS and PKC in model group were superior to those in control group at 4 weeks,but ET level reduced.Compared with control group,expression of PKC and ET increased,but NO and NOS levels decreased at 8 weeks.NO and NOS levels at 4 weeks,and Ccr,UAE,PKC expression at 8 weeks were significantly lower in experiment group than those in model group.Furthermore,there existed the improvement of renal function and pathology and downregulation of ET and TGF-β1 expression in experiment group.Conclusion PJ34 plays a renal protective role in diabetic rats,which could be mediated by inhibition of PKC and NO production and downregulation of ET and TGF-β1 expression.更多还原