川芎嗪与氨基胍联合治疗对n0-STZ大鼠肾功能的影响  

Tetramethylpyrazine combined with aminoguanidine improves renal functions in n0-STZ Wistar rats

作　　者：窦橙云[1] 王蔚琛[2] 曹创杰[1] 魏树珍[3] 李瑞峰[1] 

机构地区：[1]山东大学医学院病理生理学研究所,山东济南250012 [2]滨州医学院病理生理学教研室,山东烟台264003 [3]济南市中心医院妇产科,山东济南250013

出　　处：《中国病理生理杂志》2011年第10期1938-1943,共6页Chinese Journal of Pathophysiology

基　　金：山东省自然科学基金资助项目(No.Y2006C27);山东省卫生厅资助项目(No.99CA1CAA11)

摘　　要：目的:研究川芎嗪与氨基胍的联合治疗对新生链脲佐菌素糖尿病大鼠(n0-STZ)肾功能的影响。方法:出生当日Wistar大鼠,一次性腹腔内注射STZ诱导n0-STZ大鼠模型。实验大鼠分4组:(1)正常对照组;(2)胰岛素抵抗组;(3)二甲双胍组;(4)川芎嗪与氨基胍联合治疗组。第32周检测空腹血糖(FPG)、空腹血浆胰岛素(FINS)、胰岛素抵抗指数(IRI)、血尿素氮(BUN)、肌酐(Cr)、尿蛋白和肾小球滤过率(GFR),外周血白细胞诱导型一氧化氮合酶(iNOS)mRNA表达,肾组织中NO浓度和iNOS活性以及iNOS和3-硝基酪氨酸(3-NT)的蛋白表达。结果:(1)造模第8周,82.5%的Wistar大鼠空腹血糖≥7.0 mmol/L,肾功能受损。(2)两种治疗均能降低FPG、FINS、IRI,以联合治疗组提高胰岛素敏感性更显著;两种治疗方案都能改善大鼠肾功能,联合治疗组降低血BUN、Cr,提高肾小球滤过功能作用更强。(3)两种治疗都能下调iNOS活性和NO浓度,抑制肾组织中3-NT和iNOS表达,联合治疗组效果更显著。结论:二甲双胍和川芎嗪与氨基胍联合治疗都能通过抑制硝基化应激改善肾功能,但川芎嗪与氨基胍保护肾功能的作用优于二甲双胍。AIM：To investigate the effects of tetramethylpyrazine combined with aminoguanidine on the renal functions of neonatal-0 streptozotocin-induced（n0-STZ） rats.METHODS： Neonatal Wistar rats were intraperitoneally injected with a single dose of streptozotocin（STZ） to establish the n0-STZ rat model.The n0-STZ rats were divided into 4 groups： normal control group,insulin resistance group,metformin treatment group and tetramethylpyrazine＋aminoguanidine treatment group.Fasting plasm glucose,fasting insulin,insulin resistance index,blood urea nitrogen,serum creatinine,urine albumin and glomerular filtration rate were measured at the 32nd week.The mRNA content of inducible nitric oxide synthase（iNOS） in peripheral blood leukocytes was detected by the technique of in situ hybridization.Nitric oxide（NO） concentration,iNOS activity,the protein expression of iNOS and 3-nitrotyrosine（3-NT） were also assessed in the renal tissues.RESULTS： At the 8th week after the administration of STZ,82.5% of Wistar rats showed that the fasting plasm glucose level was ≥7.0 mmol/L and the renal functions were seriously damaged.Although both metformin and the combined treatment reduced fasting plasm glucose,fasting insulin and insulin resistance index,the combined treatment was superior in improving the insulin resistance.The damaged renal functions were improved by the combined treatment as reducing blood urea nitrogen and creatinine,increasing glomerular filtration rate were observed.Furthermore,the combined treatment reduced NO concentration,decreased iNOS activity and diminished mRNA content of iNOS,resulting in depressing the generation of 3-NT and iNOS,which surpassed the treatment of metformin.CONCLUSION： Tetramethylpyrazine combined with aminoguanidine improves the renal functions of n0-STZ rats by depressing nitrative stress and enhancing the effect of metformin.

关 键 词：胰岛素抵抗 川芎嗪与氨基胍 一氧化氮 诱导型一氧化氮合酶 3-硝基酪氨酸 

分 类 号：R363[医药卫生—病理学]