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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。
Objective: To observe the effect of Irb on the expression of connective tissue growth factor (CTGF) and p27k ip1 in diabetic rat model. Methods: SD rats were divided into healthy control group (group C), diabetic nephropathy group (DN group) and diabetic nephropathy Irb treatment group (DNI group), DN group and DNI group were made diabetic model, DNI group were given 50 mg.kg-1 irbesartan gavage. The rats in each group were further divided into 4 subgroups and were sacrificed at 1, 2, 4, and 8 weeks after the model was established respectively. The blood glucose, body weight, urinary albumin 24 h, creatinine clearance ( Ccr, renal weight, renal hypertrophy index, glomerular area (AG) and volume (VG), tubule area (AT), thickness of glomerular basement membrane (GBM) and tubule basement membrane The expression of renal CTGF and p27k ip1 was observed by immunohistochemistry. Results: The blood glucose of DN group and DNI group was significantly higher than that of C group and maintained at a higher level (P <0.01). The body weight of group C increased rapidly. The body weight of DN group and DNI group increased slowly (P <0.01). 24 h urinary albumin, Ccr, kidney weight, renal hypertrophy index, AT and VG in DN group increased in the early stage of diabetes mellitus (P <0.01 or P <0.05). Immunohistochemical semiquantitative analysis showed that the expression of CTGF and p27k ip1 in glomerulus and tubule in DN group were higher than those in C group (P <0.01 or P <0.05). At 8 weeks, GBM and TBM in DN group were significantly thicker than those in C group (P <0.01), while Irb significantly inhibited the above parameters. CTGF and p27k ip1 expression, 24 h urinary albumin, AT, AG, VG showed a significant positive correlation (P <0.05). CONCLUSION: Early use of Irb can inhibit the early renal hypertrophy and the expression of CT-GF and p27k ip1 in diabetic rats, which provides a new theoretical basis for the early use of this drug in preventing DN renal hypertrophy.