摘要
目的观察托拉塞米对大鼠肾纤维化的影响,探讨其作用机制。方法雄性SD大鼠30只,随机分为对照组6只,其余大鼠以5/6肾切除方法诱导成为慢性肾纤维化模型,分为模型组7只,用药一组和用药二组各6只(手术及用药过程中共死亡5只),分别腹腔注射托拉塞米0.3,1.0 mg.kg-1.d-1,qd,共12周后处死大鼠,检测各组大鼠血肌酐、尿素氮、血糖、血钾及血尿酸,观察并评估肾小球硬化和间质损害程度,并用RT-PCR法检测肾组织转化生长因子β1(TGF-β1)及Ⅰ型纤溶酶原激活物抑制药(PAI-1)mRNA的表达。结果用药组的肾功能优于模型组,残肾病理改变也明显减轻,且无明显不良反应,TGF-β1及PAI-1mRNA表达也较模型组明显下降。结论托拉塞米可改善5/6肾切除大鼠肾功能及肾脏病理改变,其肾脏保护作用可能与其抑制TGF-β1及PAI-1的过度表达有关,并存在一定的剂量依赖性。
Objective To study the effects of torasemide on the chronic renal fibrosis in 5/6 nephrectomiged rats and to probe into the possible mechanisms. Methods 30 male Wistar rats were randomly divided into 4 groups ： （1） the control group （ n = 6）, （2） model group （ n = 7 ）, （3）drug treatment group A （ n = 6 ） and （4） drug treatment group S （ n = 6 ）. A model of chronic renal filrosis was set up in each of the rats of group （2） to group （4） by 5/6 nephrectomy. Rats of group （3） and group （4） were given each 0.3 and 1.0 mg · kg^-1 of torasemide administered by intraperitoneal injection q.d. for 12 consecutive weeks. The animals were then sacrificed and serum creatinine, blood urea nitrogen, blood sugar, serum potassium and serum uric acid were determined. The extent of renal fibrosis and interstitial lesions in the remmant kidneys of the rats of group （2） to group （4） was kept under observation and assessment. RT-PCR was used to assay the expression of TGF-β1 （ transforming growth faclor β1 ） and PAI-I （plasminogen activator inhibitor I） mRNA in the remnatnt kidneys. Results The renal function in rats of group （3） and group （4） treated with torasemide was shown to be evidently superior to that in rats of the model group（ group 2）. Pathological changes were much more trifling in the remnatnt kidneys of rats treated with torasemide as compared with those in rats of the model group. No major adverse reactions in the drug-treated animals were encountered. The expression of TGF-β1 mRNA and PAI-1 mRNA was much less prominent in the remnant kidneys of the rats treated with torasemide than that in rats of the model group. Conclusion Torasemide was shown to improve the renal function and alleviate pathological changes in the remnant kidney of the 5/6 nephrectomiged rats in a relatively dose deperdent manner possibly by inhibiting the over-expression of TGF-β1 and PAI-1 in the remnant kidney.
出处
《医药导报》
CAS
2007年第12期1395-1397,共3页
Herald of Medicine
