厄贝沙坦对STZ诱导的糖尿病大鼠肾脏CTGF、p27kip1表达的影响

目的:观察厄贝沙坦(Irb)对大鼠糖尿病模型肾脏结缔组织生长因子(CTGF)、p27k ip1表达的影响。方法:将SD大鼠分为健康对照组(C组)、糖尿病肾病组(DN组)和糖尿病肾病Irb治疗组(DNI组),DN组和DNI组大鼠制成糖尿病模型,DNI组予以50 mg.kg-1伊贝沙坦灌胃。各组大鼠再分为4个亚组,分别于成模后1、2、4、8周时处死,观察各组大鼠的血糖、体重、24 h尿白蛋白、内生肌酐清除率(Ccr)、肾重、肾脏肥大指数、肾小球面积(AG)和体积(VG)、肾小管面积(AT)、肾小球基底膜(GBM)厚度、肾小管基底膜(TBM)厚度的改变,通过免疫组化观察肾CTGF和p27k ip1的表达。结果:DN组和DNI组大鼠血糖较C组明显升高且维持在一个较高水平(P<0.01)。C组体重增长迅速,DN组和DNI组大鼠体重增长缓慢(P<0.01)。DN组大鼠的24 h尿白蛋白、Ccr、肾重、肾脏肥大指数、AT和VG在糖尿病早期即呈时间依赖性增加(P<0.01或P<0.05)。免疫组化半定量分析显示,各期DN组大鼠肾小球和肾小管的CTGF、p27k ip1表达均高于C组(P<0.01或P<0.05)。8周时DN组大鼠GBM和TBM均较C组明显增厚(P<0.01),而Irb可显著抑制上述参数的增加。CTGF与p27k ip1的表达、24 h尿白蛋白、AT、AG、VG呈显著正相关关系(P<0.05)。结论:早期应用Irb可抑制糖尿病大鼠早期肾脏肥大和CT-GF与p27k ip1的表达,此为早期使用该药预防DN肾脏肥大的发生提供了新的理论依据。

Effects of irbesartan on the renal expressions of CTGF and p27kip1 in streptozotocin-induced diabetic rats

Objective To observe the effects of irbesartan (Irb) on the renal expressions of CTGF and p27kip1 in STZ-induced diabetic rats.Methods SD rats were randomly divided into group C,group DN and group DNI.Each group was re-divided into 4 subgroupsand were sacrificedat 1, 2,4 and 8 weeks after the diabetes was induced.Blood glucose(BG),body weight(BW),24-hour urinary albumin excretion(24 h Ualb),creatinine clearance(Ccr),kidney weight(KW),index of kidney hypertrophy(KW/BW) were determined when the rats were sacrificedby the end of experiment.Glomerular tuft area(A_(G)),glomerular volume(V_(G)),proximal tubular area(A_(T)) at each time point,thickness of glomerular basement membrane(GBM) and tubular basement membrane(TBM) at the 8th week were measured by CMIAS(RY-2000).Renal expression of CTGF and p27kip1 were detected by immunohistochemistry staining(SP method).(Results) The levels of group DN and group DNI rats' BG were higher than group C,while their BW were lower than group C.The rats of group DN had much higher 24 hUalb,Ccr,KW,KW/BW,A_(G),V_(G),A_(T),GBM,TBM and the expressions of CTGF and p27kip1 than control rats,while Irb could inhibit the increase of those parameters.(Conclusion) At the early stage of diabetes Irb can inhibit the renal hypertrophy and the expressions of renal CTGF and p27kip1.