来氟米特对糖尿病大鼠葡萄糖转运蛋白-1 mRNA表达及细胞外基质的影响

目的：探讨来氟米特对链脲佐菌素（STZ）诱导的糖尿病大鼠肾脏葡萄糖转运蛋白-1（GLUT）mRNA表达及细胞外基质的影响及其意义。方法：采用STZ腹腔注射法建立糖尿病动物模型。将大鼠随机分为正常对照组（A组）,糖尿病组（B组）,来氟米特干预组（C组）。第4、8、12周末各组随机选取4只大鼠处死并收集标本,记录体重、右肾重、检测血糖、血肌酐、血尿素氮、血胆固醇、血三酰甘油、24h尿蛋白排泄量。用RT-PCR方法检测肾皮质GLUT-1 mRNA表达水平。肾组织行HE、PAS染色,并用免疫组化法检测肾组织层黏连蛋白及Ⅳ型胶原蛋白的表达情况。结果：（1）与A组相比,B组大鼠造模成功后0周,血糖明显增高（P〈0.01）,但24h尿蛋白排泄量无明显增高（P〉0.05）;4周时体重明显降低（P〈0.01）,肾重指数、尿素氮、肌酐、胆固醇、三酰甘油、24h尿蛋白排泄量、肾皮质GLUT-1 mRNA表达明显增加（P均〈0.01）;C组12周时肾皮质GLUT-1 mRNA表达量,肾重指数、肌酐已无明显增加（P〉0.05）。（2）与B组相比,C组8周时尿素氮、肌酐降低（P均〈0.05）,胆固醇、24h尿蛋白排泄量和肾皮质GLUT-1 mRNA表达量均明显下降（P均〈0.01）;12周时体重增加（P〈0.05）,肾重指数、三酰甘油明显下降（P〈0.01）。肾组织HE、PAS染色病理学观察：B组光镜下肾小球肥大,系膜细胞增生,系膜基质弥漫性的或结节性的增多,肾小球、肾小管基底膜增厚,而C组这些病理改变明显减轻。免疫组织化学染色：B组可见系膜区Ⅳ型胶原蛋白和层黏连蛋白的大量沉积,C组也可见Ⅳ型胶原蛋白和层黏连蛋白的沉积,但较B组明显减轻。结论：来氟米特能减少糖尿病大鼠尿蛋白排泄量,纠正糖尿病大鼠的脂代谢紊乱,抑制肾脏肥大、减轻肾脏的纤维化硬化程度。其机制可能与下调系膜细胞上GLUT-1 mRNA的表达量及功能活性有关,最终延?

The Effect of Leflunomide OH Renal Expression of GLUT-1 mRNA and the Extracellular Matrix in Diabetic Rats

Objective： To investigate the effects of Leflunomide on the expression of glucose transporter- 1 （GLUT- 1 ） mRNA and the extracellular matrix in the diabetic rats,and probe into its mechanism. Methods：An animal model of diabetes was established by intraperitoneal injection of STZ. Rats were randomly divided into normal control group（group A）, diabetic control group （group B） and Leflunomide treated group（group C） . Four rats of each group were randomly chosen to be sacrificed at the end of the 4th,the 8th and the 12th week. Samples were then collected, including body weighting, right kidney weight, blood sugar, serum creatinine, blood urea nitrogen, cholesterol, triglyceride, 24 - hour urinary protein excretion. Renal GLUT- 1 mRNA expression was measured with reverse transeriptase- polymerase chain reaction （RT- PCR）. Renal pathomorphology was observed by HE and PAS staining . Laminin and type IV collagen were measured with immunohistochemical techniques. Results： （1）Compared with Group A, Blood sugar was increased significantly （P〈0.01） in Group B but 24 - hour urinary protein excretion did not increased significantly （P 〉0.05）at the incipient time when the animal model of diabetes was established successfully. At the end of the 4th week, body weight was decreased significantly （P〈 0.01 ） while the kidney weight index, serum creatinine, blood urea nitrogen, cholesterol, triglyceride, 24- hour urinary protein excretion and renal GLUT- 1 mRNA expression were increased significantly （P 〈 0.01 ）. At the end of the 12th week, renal GLUT- 1 mRNA expression, the kidney weight index, serum creatinine of group C were not increased significantly（P 〉0.05）. （2） Compared with Group B, serum creatinine, and blood urea nitrogenwere decreased（P 〈 0.05） at the end of the 8th week. Cholesterol, 24 - hour urinary protein excretion and renal GLUT- 1 mRNA expression were decreased significantly （P〈0.01）. At the end of the 12th week, body weight was increased