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

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

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(en-dothelin-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 endothelialgrowth 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(P<0.05),肾组织病理损害明显减轻,而血脂,肝功能和肌酸激酶无明显改变(P>0.05)。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<0.05),下调肾组织内皮素-1 mRNA的表达(P<0.05),上调肾组织内皮型一氧化氮合酶和血管内皮生长因子mRNA的表达(P<0.05)。结论阿托伐他汀能减轻慢性肾衰竭大鼠肾脏的病理损害,改善肾功能。这种作用可能与其促进肾小球内皮细胞的修复和改善内皮功能有关。

OBJECTIVE To investigate the effects of atorvastin on function of glome1~alar endothelia cells in rats with chronic re- nal failure （CRF）. METHODS Twenty-eight male SD rats were randomly divided into 4 groups： sham operation group （control group）, CRF group （model group）, 8mg·kg^-1·d^-1atorvastin treatment group （low-dosage group） and 16 mg mg·kg^-1·d^-1torvas- tin treatment group （high-dosage group）. The model of chronic renal failure was established by a two stage 5/6 nephrectomy proee- dure. 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 e- valuated on periodic acid-schiff （PAS） stained sections. The CD34 and CD31 expressions in glomerulus were detected by immunohisto- chemistry method. The mRNA of ET1, eNOS and VEGF were detected by RT-PCR. RESULTS The Scr, BUN and urine protein lev- els 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 mR- NA 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 reno- vation of glomerulus capillary endothelium and improving function of glomerular endothehal ceils that atorvastin ameliorates renal patho- logical injury and renal function in rats with chronic renal failure.