摘要
目的探讨阿托伐他汀对链脲佐菌素诱导的糖尿病大鼠肾组织与外周血单个核细胞(PBMC)中核因子κB(NF-κB)活性的影响。方法30只雄性SD大鼠分成对照组、糖尿病组和阿托伐他汀治疗组;酶联免疫吸附法(ELISA)测定各组大鼠PBMC中NF-κB活性;免疫组化检测各组大鼠肾组织NF-κB、单核细胞趋化蛋白-1(MCP-1)。结果糖尿病大鼠PBMC和肾小球中NF-κB显著高于对照组(P<0.01)。与糖尿病大鼠相比,阿托伐他汀明显抑制NF-κB活化及MCP-1和纤黏连蛋白(FN)表达(P<0.05),减少24h尿蛋白排泄,改善肾功能及肾病理学损害。结论NF-κB在糖尿病肾病发病中具有重要作用,抑制NF-κB的活化可能是他汀类药物发挥肾脏保护作用的机制之一。
Objective To investigate the protective effect of atorvastatin on diabetic nephropathy（DN）and its mechanisms. Methods The rat diabetic model was made by the intra-peritoneal in jection of streptozocin. The rats were divided into three groups of normal control, diabetes, diabetes treated with atorvastatin （2 mg · kg^-1 · d^- 1） by gavage. Activity of nuclear factor kappa B （NF-kB） in peripheral blood mononuclear cells （PBMC） was analyzed by Enzyme-linked Immunosorbent Assay （ELISA）. Expressions of NF-kB, MCP-1 and fibronectin（FN） in renal tissue were measured by immunohisto-chemical stain, 24-hour urinary protein, and plasma creatinine （Cr） were measured. Resuits NF-kB activities in PBMC and renal tissues（RT） in diabetic rats were significantly higher than those in normal rats （2.45±0.31 vs0. 37±0. 15, as OD value in PBMC P〈0.01 ;9. 842±1. 653 vs 1. 116±0. 467 as NF-kB positive cell number in RT,P〈0.01）. While compared with diabetic rats, atorvastatin treatment significantly inhibited activation of NF-kB（0. 58±0.06 vs 2.45±0.31 ,P〈0.05 in PBMC; 4. 158±1. 552 vs 9. 842±1. 653,P〈0.05 in RT）, reduced expression of FN, decreased urine protein excretion, ameliorated mononuclear infiltration, improved renal function and pathological changes of renal histology. Conclusions These results suggest the activated NF-kB plays a pathogenic role for diabetic nephropathy. Atorvastatin treatment slows down the development of DN. The protective effect of atorvastatin on DN appears to be mediated through the inhibition of activation of NF-kB.
出处
《中国糖尿病杂志》
CAS
CSCD
北大核心
2007年第2期91-93,共3页
Chinese Journal of Diabetes
