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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 effect of atorvastatin on the function of glomerular endothelial cells in rats with chronic renal failure (CRF). Methods Twenty-eight male SD rats were randomly divided into sham operation group (control group), chronic renal failure group (model group) and atorvastatin 8 mg.kg-1.d-1 intervention group (low dose group) mg.kg-1.d-1 atorvastatin intervention group (high-dose group). Rat model of chronic renal failure was prepared by phased 5/6 nephrectomy. The intervention group was given atorvastatin normal saline, the other two groups were given the same amount of normal saline. After 8 weeks, the changes of renal function, urinary protein, blood lipid, liver function and creatine kinase in each group were detected, and the pathological changes of kidney were observed. The expressions of CD34 and CD31 in glomeruli were detected by immunohistochemistry and the expressions of en-dothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) mRNA expression in patients with acute myocardial infarction. Results The renal function of atorvastatin group was significantly improved. Serum creatinine (Scr), blood urea nitrogen (BUN) and urinary protein levels were decreased (P <0.05) (P> 0.05). However, there was no significant change in serum lipids, liver function and creatine kinase (P> 0.05). Compared with the model group, atorvastatin treatment significantly increased the expression of glomerular CD34, CD31 (P <0.05) and the expression of endothelin-1 mRNA (P <0.05) Nitric oxide synthase and vascular endothelial growth factor mRNA expression (P <0.05). Conclusions Atorvastatin can reduce the renal pathological damage and improve renal function in rats with chronic renal failure. This effect may be related to its promotion of glomerular endothelial cell repair and improve endothelial function.