阿托伐他汀对慢性肾衰竭大鼠肾小球内皮细胞功能的影响

 目的 探讨阿托伐他汀对慢性肾衰竭（chronic renal failure， CRF）大鼠肾小球内皮细胞功能的影响。方法 28只雄性SD大鼠随机分为假手术组（对照组）、慢性肾衰竭组（模型组）及8 mg·kg^-1·d^-1阿托伐他汀干预组（小剂量组）、16 mg·kg^-1·d^-1阿托伐他汀干预组（大剂量组）。采用分阶段5/6肾切除术制备大鼠慢性肾衰竭动物模型。干预组给予阿托伐他汀生理盐水灌胃，其余两组给予等量生理盐水灌胃。8周后检测各组大鼠肾功能，尿蛋白，血脂，肝功能和肌酸激酶的变化，并观察肾组织病理改变。用免疫组化检测肾小球CD34、CD31表达，用逆转录多聚酶链反应（RT-PCR）检测肾组织内皮素-1（endothelin-1， ET-1）、内皮型一氧化氮合酶（endothelial nitric oxide synthase， eNOS）和血管内皮生长因子(vascular endothelial growth factor， VEGF)mRNA的表达。结果 阿托伐他汀治疗组大鼠肾功能明显改善，表现为血肌酐（serum creatinine， Scr）、血尿素氮（blood urea nitrogen， BUN）和尿蛋白水平降低（P0.05）。与模型组比较，阿托伐他汀治疗能显著增加大鼠肾小球CD34、CD31的表达（P

Effects of Atorvastin on Function of Glomerular Endothelial Cells in Rats with Chronic Renal Failure

OBJECTIVE To investigate the effects of atorvastin on function of glomerular endothelia cells in rats with chronic renal failure(CRF).METHODS Twenty-eight male SD rats were randomly divided into 4 groups: sham operation group(control group),CRF group(model group),8 mg·kg-1·d-1 atorvastin treatment group(low-dosage group) and 16 mg·kg-1·d-1 atorvastin treatment group(high-dosage group).The model of chronic renal failure was established by a two stage 5/6 nephrectomy proeedure.The atorvastin treatment groups were given atorvastin by intragastric administration,and the other 2 groups were given sodium chloride.Serum creatinine(Scr),blood urea nitrogen(BUN),urine protein,total cholesterol(TCHO),triglycerides(TG),low density liporotein(LDL),AST,ALT and creatine kinase(CK) were measured after 8 weeks.The renal morphologic changes were evaluated on periodic acid-schiff(PAS) stained sections.The CD34 and CD31 expressions in glomerulus were detected by immunohistochemistry method.The mRNA of ET1,eNOS and VEGF were detected by RT-PCR.RESULTS The Scr,BUN and urine protein levels in atorvastin treatment groups were significantly lower than those in CRF model group(P<0.05).Reanl pathological injuries were improved by atorvastin treatment in dose-dependent manner.There were no significant differences in TCHO,TG,LDL,AST,ALT and CK levels among the 4 groups.The expressions of CD34 and CD31 protein in glomerulus,and the expressions of eNOS and VEGF mRNA in renal tissue were higher in atorvastin treatment groups than those in CRF model group.The expression of ET-1 mRNA in renal tissue were lower in atorvastin treatment groups than those in CRF model group.CONCLUSION It might be through promoting renovation of glomerulus capillary endothelium and improving function of glomerular endothelial cells that atorvastin ameliorates renal pathological injury and renal function in rats with chronic renal failure.